Wu Yuluo, Zhao Haiyang
Department of Oncology, Guangdong Medical University Affiliated Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524000, P.R. China.
Department of Oncology, Beijing Zhongguancun Hospital, Beijing 100190, P.R. China.
Oncol Lett. 2021 Nov;22(5):810. doi: 10.3892/ol.2021.13071. Epub 2021 Sep 27.
Drug resistance is a key factor affecting the treatment of gastric cancer. The resistance of gastric cancer cells to anticancer drugs, such as cisplatin (DDP), remains a major challenge to patient recovery. The present study aimed to investigate the roles of C-terminal-binding protein 1 (CTBP1) in the DDP resistance of gastric cancer cells and to determine its regulatory effect on DNA repair protein RAD51 homolog 1 (RAD51). The DDP-resistant human gastric cancer AGS and HGC cell lines, AGS/DDP and HGC-27/DDP, respectively, were established and CTBP1 expression was detected by western blotting. In addition, Cell Counting Kit-8, colony formation and flow cytometry assays were performed to detect the proliferation and apoptosis of these two cell lines following CTBP1 knockdown. The expression levels of apoptosis-related proteins were detected by western blotting. In addition, RAD51 was overexpressed in CTBP1 knockdown cells, and proliferation and apoptosis were subsequently determined using the aforementioned methods. The results demonstrated that CTBP1 expression was notably increased in DDP-resistant gastric cancer cells. Furthermore, CTBP1 knockdown suppressed the proliferation and induced the apoptosis of AGS/DDP and HGC-27/DDP cells. Notably, CTBP1 promoted RAD51 expression in DDP-resistant gastric cancer cells. Overexpression of RAD51 in CTBP1 knockdown AGS/DDP and HGC-27/DDP cells rescued the proliferation and alleviated the apoptosis of these cells. Taken together, the results of the present study suggested that CTBP1 may enhance the DDP resistance of gastric cancer cells by activating RAD51 expression, thus providing a potential novel therapy (CTBP1 knockdown) for the clinical treatment of patients with gastric cancer.
耐药性是影响胃癌治疗的关键因素。胃癌细胞对顺铂（DDP）等抗癌药物的耐药性仍然是患者康复的主要挑战。本研究旨在探讨C末端结合蛋白1（CTBP1）在胃癌细胞对DDP耐药中的作用，并确定其对DNA修复蛋白RAD51同源物1（RAD51）的调控作用。分别建立了耐DDP的人胃癌AGS和HGC细胞系，即AGS/DDP和HGC-27/DDP，并通过蛋白质印迹法检测CTBP1表达。此外，进行细胞计数试剂盒-8、集落形成和流式细胞术分析，以检测CTBP1敲低后这两种细胞系的增殖和凋亡情况。通过蛋白质印迹法检测凋亡相关蛋白的表达水平。此外，在CTBP1敲低的细胞中过表达RAD51，随后使用上述方法确定增殖和凋亡情况。结果表明，CTBP1在耐DDP的胃癌细胞中表达显著增加。此外，CTBP1敲低抑制了AGS/DDP和HGC-27/DDP细胞的增殖并诱导其凋亡。值得注意的是，CTBP1促进耐DDP胃癌细胞中RAD51的表达。在CTBP1敲低的AGS/DDP和HGC-27/DDP细胞中过表达RAD51可挽救这些细胞的增殖并减轻其凋亡。综上所述，本研究结果表明，CTBP1可能通过激活RAD51表达增强胃癌细胞对DDP的耐药性，从而为胃癌患者的临床治疗提供一种潜在的新疗法（CTBP1敲低）。
