School of Biotechnology, Banaras Hindu University, Varanasi, 221005, India.
Apoptosis. 2013 Dec;18(12):1574-85. doi: 10.1007/s10495-013-0894-7.
The present investigation was undertaken to study the effect of in vitro exposure of Colo205, colonadenocarcinoma cells, to monocarboxylate transporter inhibitor α-cyano-4-hydroxycinnamate (αCHC) on cell survival and evolution of resistance to chemotherapeutic drug cisplatin. αCHC-treated Colo205 cells showed inhibition of survival accompanied by an augmented induction of apoptosis. Changes in cell survival properties were associated with alterations in lactate efflux, pH homeostasis, expression of glucose transporters, glucose uptake, HIF-1α, generation of nitric oxide, expression pattern of some key cell survival regulatory molecules: Bcl2, Bax, active caspase-3 and p53. Pretreatment of Colo205 cells with αCHC also altered their susceptibility to the cytotoxicity of cisplatin accompanied by altered expression of multidrug resistance regulating MDR1 and MRP1 genes. This study for the first time deciphers some of the key molecular events underlying modulation of cell survival of cancer cells of colorectal origin by αCHC and its contribution to chemosensitization against cisplatin. Thus these findings will be of immense help in further research for optimizing the use of αCHC for improving the chemotherapeutic efficacy of anticancer drugs like cisplatin.
本研究旨在探讨将结肠腺癌细胞 Colo205 进行体外暴露于单羧酸转运蛋白抑制剂 α-氰基-4-羟基肉桂酸（αCHC）对细胞存活和对化疗药物顺铂耐药性演变的影响。αCHC 处理的 Colo205 细胞表现出存活抑制，同时凋亡诱导增强。细胞存活特性的变化与乳酸外排、pH 稳态、葡萄糖转运蛋白表达、葡萄糖摄取、HIF-1α、一氧化氮生成、一些关键细胞存活调节分子的表达模式的改变有关：Bcl2、Bax、活性 caspase-3 和 p53。用 αCHC 预处理 Colo205 细胞还改变了它们对顺铂细胞毒性的敏感性，同时改变了多药耐药调节基因 MDR1 和 MRP1 的表达。这项研究首次揭示了 αCHC 调节结直肠来源癌细胞存活的一些关键分子事件及其对顺铂化疗增敏的作用。因此，这些发现将对进一步研究优化 αCHC 的使用以提高顺铂等抗癌药物的化疗效果有很大帮助。
