C-terminal binding protein‑2 mediates cisplatin chemoresistance in esophageal cancer cells via the inhibition of apoptosis

Abstract

C-terminal binding protein‑2 (CtBP2) is a transcriptional co-repressor that is associated with tumorigenesis and tumor progression. It has been reported to predict a poor prognosis in several human cancers, including esophageal squamous cell carcinoma (ESCC). The present study aimed to investigate the involvement of CtBP2 in the cisplatin (DDP) resistance of the ECA109 ESCC cell line and its effect on the expression of apoptosis-associated proteins. Constructed recombinant lentiviruses were used for the knockdown or overexpression of CtBP2 in ECA109 cells, and the expression of CtBP2 was measured using reverse transcription-quantitative polymerase chain reaction and western blotting following transfection. MTT assays, Hoechst 33342 staining and flow cytometry (FCM) were applied to detect the influence of CtBP2 on the DDP-induced viability and apoptosis of the transfected ECA109 cells. In addition, the levels of apoptosis-associated proteins, including p53, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and activated caspase-3 were investigated in the transfected ECA109 cells. Stable ECA109 cells with CtBP2 overexpression or knockdown were successfully established. The results of the MTT, Hoechst 33342 and FCM assays demonstrated that overexpression of CtBP2 attenuated the reduction of cell viability and inhibited the cell apoptosis induced by DDP. Furthermore, the western blotting results indicated that CtBP2 overexpression inhibited the DDP-induced apoptosis of ECA109 cells via the reduction of p53, activated caspase-3 and Bax expression, and promotion of Bcl‑2 expression. Therefore, the present study indicated that CtBP2 reduced the susceptibility of ECA109 cells to DDP by regulating the expression of apoptosis-related proteins, suggesting that it may be a promising therapeutic target in ESCC in the future.

RETRACTED: Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway

“…In general, DDP and other platinum-based compounds are considered to be cytotoxic drugs, which can induce apoptosis of cancer cells ( 24 ). Numerous molecular anticancer mechanisms have been described, including the induction of p53 signaling and cell cycle arrest ( 25 , 26 ), downregulation of proto-oncogenes and anti-apoptotic proteins, and activation of both intrinsic and extrinsic apoptosis ( 27 , 28 ). However, DDP has also been associated with substantial side effects, including hepatotoxic, nephrotoxic, cardiotoxic, neurotoxic, and/or hematotoxic damage.…”

circRNA_001275 upregulates Wnt7a expression by competitively sponging miR‑370‑3p to promote cisplatin resistance in esophageal cancer

“…Chemotherapy is the main treatment for advanced esophageal cancer, and cisplatin-based chemotherapy is considered to be a first-line therapy (2). However, the majority of patients will benefit from cisplatin treatment for the initial 4-6 chemotherapy cycles, then subsequently develop cisplatin resistance (3,4). Cisplatin resistance is the main reason for treatment failure and mortality in patients with esophageal cancer (5).…”

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

“…3). Interestingly, KIF26B, GAS7, MIR135A, and CTBP2, all potential target genes of variants associated with the survival of BRCA1 carriers, have been suggested to modify the response to platinum-based chemotherapy [51][52][53][54][55][56] . Furthermore, CTBP2 has been shown to affect the sensitivity to PARP inhibitors by targeting the BRCA1 promoter for epigenetic silencing 50 .…”