Wang S Q, Zhang S W, Zhang C Z, Zhao Z Y, Wang Y J
Tianjin Union Medical Center, Tianjin, 300121, China.
Cell Mol Biol (Noisy-le-grand). 2017 Apr 29;63(4):53-58. doi: 10.14715/cmb/2017.63.4.9.
Oxaliplatin, a platinum-based chemotherapeutic agent, is an important first-line drug in the treatment of colorectal cancers, but drug resistance causes treatment failure. It has been reported that gap junctional communication can enhance the cytotoxicity of platinum drugs. The gap junction formed of connexin proteins provides a direct pathway for electrical and metabolic cell-cell interaction. The voltage-dependent gating of gap junction allows small hydrophilic molecules and ions to permeate to adjacent cells. Connexin 43 is a diagnostic marker for cancer therapy and the predominant connexin isoform in many cell types. The purpose of this study was to investigate the role of connexin 43 in oxaliplatin activity by using colorectal cancer cell lines. LoVo and HCT116 cell lines were used for analysis. Connexin 43 expression was confirmed by western blot and immunocytochemistry. MTT, western blot, "Parachute" dye-coupling assays and reactive oxygen species measurement were used to detect cytotoxicity and the inhibition of connexin 43 expression induced by oxaliplatin. Results showed that connexin 43 enhanced oxaliplatin cytotoxicity through gap junctional communication function and high concentration of oxaliplatin inhibited connexin 43 expression to counteract its cytotoxicity. This study suggested that connexin 43 could be considered a molecular target of oxaliplatin activity in colorectal cancer.
奥沙利铂是一种铂类化疗药物，是治疗结直肠癌的重要一线药物，但耐药性会导致治疗失败。据报道，间隙连接通讯可增强铂类药物的细胞毒性。由连接蛋白形成的间隙连接为细胞间的电和代谢相互作用提供了直接途径。间隙连接的电压依赖性门控允许小的亲水分子和离子渗透到相邻细胞。连接蛋白43是癌症治疗的诊断标志物，也是许多细胞类型中主要的连接蛋白亚型。本研究的目的是通过使用结直肠癌细胞系来研究连接蛋白43在奥沙利铂活性中的作用。使用LoVo和HCT116细胞系进行分析。通过蛋白质免疫印迹法和免疫细胞化学法确认连接蛋白43的表达。采用MTT法、蛋白质免疫印迹法、“降落伞”染料偶联试验和活性氧测量来检测细胞毒性以及奥沙利铂诱导的连接蛋白43表达的抑制情况。结果表明，连接蛋白43通过间隙连接通讯功能增强奥沙利铂的细胞毒性，而高浓度的奥沙利铂会抑制连接蛋白43的表达以抵消其细胞毒性。本研究表明，连接蛋白43可被视为奥沙利铂在结直肠癌中发挥活性的分子靶点。
