CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression

Abstract

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.

Guanosine diphosphate–mannose suppresses homologous recombination repair and potentiates antitumor immunity in triple-negative breast cancer

“…Inactivation or low expression of HRR-related genes is frequently observed in breast cancer cells and might lead to HRD ( 21 ). Considering the documented functions of HRR-related proteins in human breast cancer cells ( 22 – 24 ), we performed an immunoblot analysis with cells treated with GDP-M. We observed that BRCA2 expression was reduced, whereas the expression of other HRR-related proteins was not significantly affected (Fig. 4B and fig.…”

Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness

“…CTBP1 is a transcriptional regulator of a range of developmental processes and promotes cancer progression. 202 , 203 , 204 , 205 However, its role in T cell differentiation is unknown. Our transcriptomic data suggest that upon chronic stimulation, Ctbp1 inactivation pushes cells into a relatively active state accompanied by stalled terminal differentiation.…”

The Implication of Topoisomerase II Inhibitors in Synthetic Lethality for Cancer Therapy

“…The most common mutations in the HR pathway occur in the BRCA1, BRCA2, RAD51, BLM, and RAD50 genes [ 74 ]. RAD51 overexpression has been linked to worse prognosis in patients with sporadic gastric cancer and neuroblastoma who present modified MRE11 [ 75 , 76 ]. In contrast, RAD50 and NBS1 mutations are associated with carcinogenesis during endometrial and prostate cancer development [ 77 , 78 ].…”