摘要
Cisplatin (CDDP), a platinum-containing drug, has been widely used in the therapy of many types of cancers today. However, the side effects of CDDP have limited its clinical application. Butaselen (BS), a TrxR inhibitor designed by our group, has shown anti-tumor effects in vivo and in vitro. In this study, we investigated the combinatory effects of BS and CDDP on BEL-7402 cells, LoVo cells, HeLa cells and A549 cells. We observed synergistic effects when BS and CDDP were used in combination, especially in BEL-7402 cells. Apoptosis analysis also revealed that the combination treatment of BS and CDDP (1:1) for 48 h induced higher apoptotic effects in BEL-7402 cells. A further study in BEL-7402 cells showed that the synergistic effect might be mediated by the sharp reduction of ratio of Bcl-2/Bax protein. Taken together, the combination of CDDP and BS might be of great potential for chemotherapy.
顺铂是一种含铂药物,目前已被广泛应用于多种癌症的治疗。然而,顺铂的副作用限制了其在临床的应用。丁烷硒啉(BS)是我们实验室自主设计的Trx R抑制剂,在体内和体外均显示出抗肿瘤作用。在本研究中,我们考察了丁烷硒啉和顺铂在BEL-7402细胞,Lo Vo细胞,He La细胞和A549细胞中的联合作用。丁烷硒啉和顺铂联合给药时具有协同作用,尤其是BEL-7402细胞。细胞凋亡分析显示,在BEL-7402细胞中,丁烷硒啉和顺铂联合(1:1)给药48小时能够诱导更高的凋亡效应。在BEL-7402细胞中的进一步研究表明,协同作用可能是Bcl-2/Bax蛋白表达比例急剧下降所致。总之,顺铂与丁烷硒啉联用可能是化疗治疗中有应用前景的策略之一。
基金
The National Natural Science Foundation(Grant No.81372266)
National Science and Technology Major Project,People’s Republic of China(Grant No.2011zx09101-001-03)