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Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma. Sirtuin1(sirt1)调节糖酵解途径并降低顺铂化疗对食管鳞状细胞癌的敏感性。
IF 4.4 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-06-12 DOI: 10.1080/15384047.2024.2365449
Xuewen Yang, Shisen Li, Chunsheng Xu, Shushang Liu, Xiang Zhang, Bo Lian, Mengbin Li

We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.

我们旨在评估sirtuin1(sirt1)对ESCC顺铂化疗敏感性的影响。我们使用 ESCC 细胞消融 sirt1 来建立异种移植小鼠肿瘤模型,然后检测肿瘤体积。sirt1在ESCC患者和细胞中显著过度表达。此外,sirt1的敲除提高了ESCC对顺铂的敏感性。此外,糖酵解与 ESCC 细胞对顺铂的化疗耐药性有关。此外,sirt1通过HK2增加了ESCC细胞对顺铂的化疗敏感性。Sirt1增强了体内ESCC对顺铂的化疗敏感性。总之,这些研究结果表明,sirt1的敲除调节了糖酵解途径,提高了ESCC的化疗敏感性。
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引用次数: 0
MiR-135b-5p promotes cetuximab resistance in colorectal cancer by regulating FOXN3. MiR-135b-5p 通过调控 FOXN3 促进结直肠癌对西妥昔单抗的耐药性
IF 4.4 4区 医学 Q2 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-07-05 DOI: 10.1080/15384047.2024.2373497
Chun Peng, Xiaoqing Li, Yuhui Yao, Yu Nie, Lingyao Fan, Chuandong Zhu

Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According to reports, the development of CRC is linked to miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between CRC tissues and adjacent tissues. However, it is unclear whether there is a correlation between miR-135b-5p and cetuximab (CTx) resistance in CRC. Use the GEO database to measure miR-135b-5p expression in CRC. Additionally, RT-qPCR was applied to ascertain the production level of miR-135b-5p in three human CRC cells and NCM460 cells. The capacity of cells to migrate and invade was examined utilizing the wound-healing and transwell assays, while the CCK-8 assay served for evaluating cell viability, as well as colony formation assays for proliferation. The expected target protein of miR-135b-5p in CRC cell cetuximab resistance has been investigated using western blot. Suppression of miR-135b-5p could increase the CTx sensitivity of CTx-resistant CRC cells, as manifested by the attenuation of proliferation, migration, and invasion ability. Mechanistic studies revealed miR-135b-5p regulates the epithelial-to-mesenchymal transition (EMT) process and Wnt/β-catenin signaling pathway through downgulating FOXN3. In short, knockdowning miR-135b-5p could increase FOXN3 expression in CRC cells, promote the EMT process, and simultaneously activate the Wnt/β-catenin signaling pathway to elevate CTx resistance in CRC cells.

尽管靶向疗法取得了进展,但原发性和获得性耐药性使结直肠癌(CRC)的治疗成为亟待解决的问题。据报道,CRC 的发病与 miRNA 失调有关。多项研究表明,miR-135b-5p 在 CRC 组织和邻近组织之间存在异常表达水平。然而,miR-135b-5p 与西妥昔单抗(CTx)在 CRC 中的耐药性之间是否存在相关性尚不清楚。利用 GEO 数据库测量 CRC 中 miR-135b-5p 的表达。此外,还应用 RT-qPCR 来确定 miR-135b-5p 在三种人类 CRC 细胞和 NCM460 细胞中的产生水平。利用伤口愈合和透孔试验检测了细胞的迁移和侵袭能力,CCK-8 试验评估了细胞的存活率,而菌落形成试验则检测了细胞的增殖情况。利用 Western 印迹法研究了 miR-135b-5p 在 CRC 细胞西妥昔单抗耐药性中的预期靶蛋白。抑制miR-135b-5p可增加CTx耐药的CRC细胞对CTx的敏感性,表现为增殖、迁移和侵袭能力的减弱。机理研究发现,miR-135b-5p通过下调FOXN3调节上皮细胞向间质转化(EMT)过程和Wnt/β-catenin信号通路。总之,敲除 miR-135b-5p 可增加 CRC 细胞中 FOXN3 的表达,促进 EMT 过程,同时激活 Wnt/β-catenin 信号通路,从而提高 CRC 细胞对 CTx 的耐药性。
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引用次数: 0
Prognostic value of pretreatment procalcitonin and neutrophil-lymphocyte ratio in extensive-stage small-cell lung cancer. 广泛期小细胞肺癌治疗前降钙素原和中性粒细胞-淋巴细胞比值的预后价值
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-27 DOI: 10.1080/15384047.2024.2331273
Dongfang Chen, Jianlin Xu, Yizhuo Zhao, Baohui Han, Runbo Zhong

Background: To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients.

Method: A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤3.17), high NLR group (NLR>3.17), low PCT group (PCT ≤0.06; ng/ml), high PCT group (PCT>0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS.

Results: The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; p = .675). Patients with low pretreatment PCT (PCT ≤0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT>0.06; ng/ml) (6.9 months vs 5.7 months; p = .043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (p ≤ .001) and pretreatment PCT (HR = 0.516; 95%CI 0.326-0.817; p = .005) were identified as independent factors associated with PFS.

Conclusion: Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.

研究背景目的:探讨治疗前中性粒细胞与淋巴细胞比值(NLR)和降钙素原(PCT)对广泛期小细胞肺癌(SCLC)患者无进展生存期(PFS)的影响:我们的研究共招募了100名广泛期小细胞肺癌(SCLC)患者。根据治疗前NLR和PCT水平的中位值对患者进行分层:低NLR组(NLR≤3.17)、高NLR组(NLR>3.17)、低PCT组(PCT≤0.06;ng/ml)、高PCT组(PCT>0.06;ng/ml)。采用Kaplan-Meier方法和多变量Cox回归模型揭示治疗前NLR和PCT对PFS的预后影响:结果:所有广泛期SCLC患者的中位PFS为6.0个月。低NLR组(NLR≤3.17)的中位生存期与高NLR组(6.2个月 vs 5.8个月;P = .675)无显著差异。治疗前PCT较低的患者(PCT≤0.06;ng/ml)的PFS明显优于治疗前PCT较高的患者(PCT>0.06;ng/ml)(6.9个月 vs 5.7个月;p = .043)。通过多变量考克斯回归分析,发现对一线化疗的反应(p ≤ .001)和治疗前PCT(HR = 0.516; 95%CI 0.326-0.817; p = .005)是与PFS相关的独立因素:结论:对于接受一线化疗的广泛期SCLC患者而言,治疗前PCT是与PFS相关的独立因素,但在我们的研究中,治疗前NLR并不具有显著的预后价值。
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引用次数: 0
WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα. WYC-209 通过 RARα 下调 WNT4,从而抑制 GC 的恶性发展。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-01-04 DOI: 10.1080/15384047.2023.2299288
Zhenyuan Qian, Wenfa Lin, Xufan Cai, Jianzhang Wu, Kun Ke, Zaiyuan Ye, Fang Wu

Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα.

胃癌(GC)一直是全球主要的健康负担,但由于其多药耐药性,有前景的化疗药物较少。有报道称,WYC-209 可抑制肿瘤繁殖细胞的生长和转移,但对 GC 的影响尚未探究。为了研究 WYC-209 对 GC 细胞的增殖、集落生长和移动性的影响,我们进行了 MTT、集落形成和透孔试验。采用 Western 印迹和 qRT-PCR 检测蛋白质和 mRNA 的表达。对差异表达基因和富集的生物过程和通路进行了 RNA-seq 和富集分析。为了进一步验证,我们还进行了拯救实验。此外,我们还构建了异种移植模型来证实 WYC-209 在体内的作用。我们还利用双荧光素酶报告和染色质免疫沉淀来证实其潜在机制。WYC-209在体外和体内都发挥了很好的抗癌作用。基于 RNA-seq 和富集分析,我们发现 Wnt 家族成员 4(WNT4)被显著下调。更重要的是,WNT4的过表达破坏了WYC-209对GC进展的抑制作用。在机制上,WYC-209 能明显促进视黄酸受体α(RARα)与 WNT4 启动子的结合。WYC-209 通过 RARα 下调 WNT4 的表达,从而在 GC 中发挥抗肿瘤作用。
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引用次数: 0
Association between the apoptotic effect of Cabazitaxel and its pro-oxidant efficacy on the redox adaptation mechanisms in prostate cancer cells with different resistance phenotypes. 卡巴他赛的凋亡效应及其促氧化作用与不同抗性表型的前列腺癌细胞的氧化还原适应机制之间的联系
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-14 DOI: 10.1080/15384047.2024.2329368
Isil Ezgi Eryilmaz, Unal Egeli, Gulsah Cecener

Redox adaptation causes poor prognosis by adapting cancer cells to excessive oxidative stress. Previously, we introduced an oxidative stress-resistant metastatic prostate cancer (mPC) model (LNCaP-HPR) that redox adaptation reduced the effect of Cabazitaxel (Cab), the last taxane-derivative for metastatic castration-resistant PC (mCRPC). Whereas, we investigated for the first time whether there is an association between the altered apoptotic effect and pro-oxidant efficacy of Cab on the redox adaptation in PC cells with different phenotypes, including LNCaP mPC, LNCaP-HPR, C4-2 mCRPC, and RWPE-1 cells. Cab was shown pro-oxidant efficacy proportionally with the apoptotic effect, more prominent in the less aggressive LNCaP cells, by increasing the endogenous ROS, mitochondrial damage, and inhibiting nuclear ROS scavengers, p-Nrf2 and HIF-1α. However, the pro-oxidant and apoptotic effect was lower in the LNCaP-HPR and C4-2 cells, indicating that the drug sensitivity of the cells adapted to survive with more ROS was reduced via altered regulation of redox adaptation. Additionally, unlike LNCaP, Cab caused an increase in the p-NF-κB activation, suggesting that the p-NF-κB might accompany maintaining survival with the increased ROS in the aggressive PC cells. Moreover, the cytotoxic and apoptotic effects of Cab were less on RWPE-1 cells compared to LNCaP but were closer to those on the more aggressive LNCaP-HPR and C4-2 cells, except for the changing pro-oxidant effect of Cab. Consequently, this study indicates the variable pro-oxidant effects of Cab on redox-sensitive proteins, which could be a target for improving Cab's apoptotic effect more in aggressive PC cells.

氧化还原适应使癌细胞适应过度氧化应激,从而导致不良预后。此前,我们引入了一种氧化应激耐受性转移性前列腺癌(mPC)模型(LNCaP-HPR),该模型的氧化还原适应性降低了卡巴他赛(Cabazitaxel)的作用,而卡巴他赛是治疗转移性阉割耐药PC(mCRPC)的最后一种类固醇衍生物。因此,我们首次研究了在不同表型的 PC 细胞(包括 LNCaP mPC、LNCaP-HPR、C4-2 mCRPC 和 RWPE-1 细胞)中,Cab 的凋亡效应改变和促氧化功效是否与氧化还原适应有关。通过增加内源性 ROS、线粒体损伤以及抑制核 ROS 清除剂 p-Nrf2 和 HIF-1α ,Cab 的促氧化作用与细胞凋亡作用成正比,在侵袭性较低的 LNCaP 细胞中更为突出。然而,LNCaP-HPR 和 C4-2 细胞的促氧化和凋亡效应较低,这表明适应在更多 ROS 下生存的细胞通过改变氧化还原适应性的调节降低了对药物的敏感性。此外,与 LNCaP 不同的是,Cab 会导致 p-NF-κB 活化增加,这表明 p-NF-κB 可能伴随着侵袭性 PC 细胞中 ROS 的增加而维持生存。此外,与 LNCaP 细胞相比,Cab 对 RWPE-1 细胞的细胞毒性和凋亡效应较小,但对侵袭性较强的 LNCaP-HPR 和 C4-2 细胞的细胞毒性和凋亡效应则较为接近,只是 Cab 的促氧化效应发生了变化。因此,这项研究表明,Cab 对氧化还原敏感蛋白的促氧化作用是可变的,这可能是提高 Cab 对侵袭性 PC 细胞的凋亡效应的一个目标。
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引用次数: 0
Epigenetic silencing ZSCAN23 promotes pancreatic cancer growth by activating Wnt signaling. 表观遗传沉默 ZSCAN23 通过激活 Wnt 信号促进胰腺癌生长
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-01-16 DOI: 10.1080/15384047.2024.2302924
Qian Du, Meiying Zhang, Aiai Gao, Tao He, Mingzhou Guo

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant tumor. Zinc finger and SCAN domain-containing protein 23 (ZSCAN23) is a new member of the SCAN domain family. The expression regulation and biological function remain to be elucidated. In this study, we explored the epigenetic regulation and the function of ZSCAN23 in PDAC. ZSCAN23 was methylated in 60.21% (171/284) of PDAC and its expression was regulated by promoter region methylation. The expression of ZSCAN23 inhibited cell proliferation, colony formation, migration, invasion, and induced apoptosis and G1/S phase arrest. ZSCAN23 suppressed Panc10.05 cell xenograft growth in mice. Mechanistically, ZSCAN23 inhibited Wnt signaling by interacting with myosin heavy chain 9 (MYH9) in pancreatic cancer cells. ZSCAN23 is frequently methylated in PDAC and may serve as a detective marker. ZSCAN23 suppresses PDAC cell growth both in vitro and in vivo.

胰腺导管腺癌(PDAC)是恶性程度最高的肿瘤。锌指和含 SCAN 结构域蛋白 23(ZSCAN23)是 SCAN 结构域家族的新成员。其表达调控和生物学功能仍有待阐明。本研究探讨了ZSCAN23在PDAC中的表观遗传调控及其功能。在60.21%(171/284)的PDAC中,ZSCAN23被甲基化,其表达受启动子区甲基化调控。ZSCAN23的表达可抑制细胞增殖、集落形成、迁移和侵袭,并诱导细胞凋亡和G1/S期停滞。ZSCAN23抑制了Panc10.05细胞在小鼠体内的异种移植生长。从机理上讲,ZSCAN23通过与胰腺癌细胞中的肌球蛋白重链9(MYH9)相互作用来抑制Wnt信号转导。ZSCAN23在PDAC中经常发生甲基化,可作为一种检测标记物。ZSCAN23 在体外和体内都能抑制 PDAC 细胞的生长。
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引用次数: 0
M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells. M6A 修饰调节宫颈癌细胞中肿瘤抑制因子 DIRAS1 的表达。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-02-19 DOI: 10.1080/15384047.2024.2306674
Yu-Yan Wang, Lian-Hua Ye, An-Qi Zhao, Wei-Ran Gao, Ning Dai, Yu Yin, Xin Zhang

DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.

据报道,DIRAS 家族 GTPase 1(DIRAS1)在其他人类癌症中是一种潜在的肿瘤抑制因子。然而,它在宫颈癌中的表达模式和作用仍然未知。敲除 DIRAS1 能显著促进体外培养的 C33A 和 SiHa 细胞的增殖、生长、迁移和侵袭。过表达 DIRAS1 能明显抑制 C33A 和 SiHa 细胞的活力和运动。与正常宫颈组织相比,宫颈癌组织中的 DIRAS1 mRNA 水平明显较低。与癌旁组织相比,宫颈癌组织中 DIRAS1 蛋白表达也明显降低。此外,肿瘤组织中 DIRAS1 的表达水平与宫颈癌患者的病理分级呈明显负相关。DNA 甲基化抑制剂(5-氮杂胞嘧啶)和组蛋白去乙酰化抑制剂(SAHA)会导致 C33A 和 SiHa 细胞中 DIRAS1 mRNA 水平的显著增加,但不会影响 DIRAS1 蛋白水平。FTO 抑制剂(FB23-2)可显著下调细胞内 DIRAS1 mRNA 水平,但可显著上调 DIRAS1 蛋白水平。此外,下调 METTL3 和 METTL14 的表达可明显抑制 DIRAS1 蛋白的表达,而下调 FTO 和 ALKBH5 的表达可明显增加 DIRAS1 蛋白的表达。总之,DIRAS1 在宫颈癌细胞中具有明显的抗癌功能,且其表达明显下调。m6A 修饰可能是调控宫颈癌中 DIRAS1 mRNA 稳定性和蛋白翻译效率的关键机制。
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引用次数: 0
Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer. 亚油酸在子宫内膜癌细胞和子宫内膜癌转基因模型中具有抗增殖和抗侵袭活性。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-11 DOI: 10.1080/15384047.2024.2325130
Jianqing Qiu, Ziyi Zhao, Hongyan Suo, Sarah E Paraghamian, Gabrielle M Hawkins, Wenchuan Sun, Xin Zhang, Tianran Hao, Beor Deng, Xiaochang Shen, Chunxiao Zhou, Victoria Bae-Jump

Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.

新出现的证据使人们对脂肪酸代谢重编程在子宫内膜癌的发生和发展过程中的整体功能有了更深入的了解。亚油酸是西方膳食中消耗量最高的一种必需脂肪酸,在多种癌症中对肿瘤细胞的生长和侵袭具有促癌或抗癌作用。然而,亚油酸在子宫内膜癌中的生物学作用仍不清楚。本研究旨在探讨亚油酸对子宫内膜癌细胞和子宫内膜癌转基因小鼠模型的细胞增殖、侵袭和肿瘤生长的功能性影响。结果表明,亚油酸以剂量依赖的方式显著抑制了子宫内膜癌细胞的增殖。亚油酸处理HEC-1A和KLE细胞能有效增加细胞内活性氧(ROS)的产生,降低线粒体膜电位,导致细胞周期G1停滞,并诱导细胞内、外凋亡通路。研究发现,亚油酸的抗侵袭能力与两种细胞系的上皮-间质转化过程有关,包括N-钙粘连蛋白、蜗牛和波形蛋白的表达减少。此外,用亚油酸治疗Lkb1fl/flp53fl/fl转基因小鼠四周,可显著减少子宫内膜肿瘤的生长,并降低肿瘤组织中血管内皮生长因子、波形蛋白、Ki67和细胞周期蛋白D1的表达。我们的研究结果表明,亚油酸在子宫内膜癌细胞系和Lkb1fl/flp53fl/fl子宫内膜癌小鼠模型中具有抗增殖和抗侵袭活性,从而为今后用亚油酸对子宫内膜癌进行膳食干预提供了临床前基础。
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引用次数: 0
The critical role of tumor microbiome in cancer immunotherapy. 肿瘤微生物组在癌症免疫疗法中的关键作用。
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-01-19 DOI: 10.1080/15384047.2024.2301801
Liu Yang, Qi Wang, Lijuan He, Xingyu Sun

In recent years, the microbiome has shown an integral role in cancer immunotherapy and has become a prominent and widely studied topic. A full understanding of the interactions between the tumor microbiome and various immunotherapies offers opportunities for immunotherapy of cancer. This review scrutinizes the composition of the tumor microbiome, the mechanism of microbial immune regulation, the influence of tumor microorganisms on tumor metastasis, and the interaction between tumor microorganisms and immunotherapy. In addition, this review also summarizes the challenges and opportunities of immunotherapy through tumor microbes, as well as the prospects and directions for future related research. In conclusion, the potential of microbial immunotherapy to enhance treatment outcomes for cancer patients should not be underestimated. Through this review, it is hoped that more research on tumor microbial immunotherapy will be done to better solve the treatment problems of cancer patients.

近年来,微生物组在癌症免疫疗法中显示出不可或缺的作用,并已成为一个突出和广泛研究的课题。充分了解肿瘤微生物组与各种免疫疗法之间的相互作用为癌症免疫疗法提供了机遇。本综述仔细研究了肿瘤微生物组的组成、微生物免疫调节的机制、肿瘤微生物对肿瘤转移的影响以及肿瘤微生物与免疫疗法之间的相互作用。此外,本综述还总结了通过肿瘤微生物进行免疫治疗所面临的挑战和机遇,以及未来相关研究的前景和方向。总之,微生物免疫疗法在提高癌症患者治疗效果方面的潜力不容小觑。通过本综述,希望能有更多关于肿瘤微生物免疫疗法的研究,以更好地解决癌症患者的治疗问题。
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引用次数: 0
Role and mechanism of COL3A1 in regulating the growth, metastasis, and drug sensitivity in cisplatin-resistant non-small cell lung cancer cells. COL3A1在调节顺铂耐药非小细胞肺癌细胞的生长、转移和药物敏感性中的作用和机制
IF 3.6 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-26 DOI: 10.1080/15384047.2024.2328382
Jiankun Ren, Songwei Zhao, Junyu Lai

Non-small cell lung cancer (NSCLC) is among the most difficult malignancies to treat. Type III collagen (COL3A1) can affect the progression and chemoresistance development of NSCLC. We herein explored the mechanism that drives COL3A1 dysregulation in NSCLC. Potential RNA-binding proteins (RBPs) and transcription factors (TFs) that could bind to COL3A1 were searched by bioinformatics. mRNA expression was detected by quantitative PCR. Protein expression was evaluated using immunoblotting and immunohistochemistry. The effects of the variables were assessed by gauging cell growth, invasiveness, migratory capacity, apoptosis, and cisplatin (DDP) sensitivity. The direct YY1/COL3A1 relationship was confirmed by ChIP and luciferase reporter experiments. Xenograft experiments were done to examine COL3A1's function in DDP efficacy. COL3A1 showed enhanced expression in DDP-resistant NSCLC. In H460/DDP and A549/DDP cells, downregulation of COL3A1 exerted inhibitory functions in cell growth, invasiveness, and migration, as well as promoting effects on cell DDP sensitivity and apoptosis. Mechanistically, ELAV-like RNA binding protein 1 (ELAVL1) enhanced the mRNA stability and expression of COL3A1, and Yin Yang 1 (YY1) promoted the transcription and expression of COL3A1. Furthermore, upregulation of COL3A1 reversed ELAVL1 inhibition- or YY1 deficiency-mediated functions in DDP-resistant NSCLC cells. Additionally, COL3A1 downregulation enhanced the anti-tumor efficacy of DDP in vivo. Our investigation demonstrates that COL3A1 upregulation, induced by both RBP ELAVL1 and TF YY1, exerts important functions in phenotypes of NSCLC cells with DDP resistance, offering an innovative opportunity in the treatment of drug-resistant NSCLC.

非小细胞肺癌(NSCLC)是最难治疗的恶性肿瘤之一。III型胶原蛋白(COL3A1)可影响非小细胞肺癌的进展和化疗耐药性的形成。我们在此探讨了NSCLC中COL3A1失调的驱动机制。通过生物信息学搜索了可能与 COL3A1 结合的潜在 RNA 结合蛋白(RBPs)和转录因子(TFs)。使用免疫印迹法和免疫组织化学法评估蛋白质表达。通过测量细胞生长、侵袭性、迁移能力、细胞凋亡和顺铂(DDP)敏感性来评估变量的影响。通过 ChIP 和荧光素酶报告实验证实了 YY1/COL3A1 的直接关系。异种移植实验检验了 COL3A1 在 DDP 疗效中的功能。COL3A1在对DDP耐药的NSCLC中表达增强。在H460/DDP和A549/DDP细胞中,下调COL3A1可抑制细胞生长、侵袭性和迁移,并促进细胞对DDP的敏感性和凋亡。从机制上看,ELAV样RNA结合蛋白1(ELAVL1)增强了COL3A1的mRNA稳定性和表达,阴阳1(YY1)促进了COL3A1的转录和表达。此外,COL3A1的上调逆转了ELAVL1抑制或YY1缺乏介导的DDP耐药NSCLC细胞的功能。此外,COL3A1的下调增强了DDP在体内的抗肿瘤功效。我们的研究表明,RBP ELAVL1和TF YY1诱导的COL3A1上调在DDP耐药的NSCLC细胞表型中发挥了重要作用,为耐药NSCLC的治疗提供了创新机会。
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Cancer Biology & Therapy
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