TXNL1 Induces Apoptosis in Cisplatin Resistant Human Gastric Cancer Cell Lines
TXNL1 Induces Apoptosis in Cisplatin Resistant Human Gastric Cancer Cell Lines
复制标题
TXNL1 诱导顺铂耐药人胃癌细胞系凋亡。
DOI：
10.2174/1568009614666141028094612
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发表时间：
2014-01-01
影响因子：
3
通讯作者：
Zhou, Jianwei
中科院分区：
文献类型：
--
作者：
Ni, Pan;Xu, Wenxia;Zhou, Jianwei
顺铂是治疗胃癌最常用的药物之一。然而，耐药性是有效治疗的主要障碍，其根源在于增强DNA修复和抗凋亡等多种机制。我们之前的结果表明，XRCC1 是顺铂诱导的 DNA 损伤和细胞凋亡的关键调节因子。 TXNL1 是硫氧还蛋白家族的成员，通过泛素-蛋白酶体途径负向调节 XRCC1 的表达。在这里，我们研究了 TXNL1 在顺铂诱导的细胞凋亡中的作用。我们的数据显示，与顺铂敏感细胞系BGC823和SGC7901相比，顺铂耐药的胃癌细胞系BGC823/DDP和SGC7901/DDP细胞中TXNL1的表达显着降低。通过 Tunel 和克隆形成实验分别检测到，BGC823 和 SGC7901 细胞中 TXNL1 表达的抑制导致对顺铂诱导的细胞凋亡和细胞死亡的抵抗力增加。相反，BGC823/DDP和SGC7901/DDP细胞中TXNL1的过度表达导致更高的顺铂诱导的细胞凋亡和细胞死亡。此外，我们的结果表明TXNL1调节顺铂诱导的细胞凋亡的机制与Bcl-2介导的线粒体凋亡途径密切相关。总之，这些发现表明 TXNL1 是人胃癌细胞顺铂耐药表型的可行调节剂和潜在化疗靶点。
Cisplatin is one of the most commonly used drugs in the treatment of gastric cancer. However, drug resistance is a major obstacle for effective treatment and originates in multiple mechanisms such as enhanced DNA repair and anti-apoptosis. Our previous results demonstrated that XRCC1 was a key regulator of cisplatin induced DNA damage and apoptosis. TXNL1, a member of the thioredoxin family, negatively regulated the expression of XRCC1 via the ubiquitin-proteasome pathway. Here, we investigated the role of TXNL1 in the apoptosis induced by cisplatin. Our data showed that the expression of TXNL1 in the cisplatin resistant gastric cancer cell lines BGC823/DDP and SGC7901/DDP cells was significantly lower compared with the cisplatin sensitive cell lines BGC823 and SGC7901. Inhibition of the expression of TXNL1 in BGC823 and SGC7901 cells led to increased resistance to cisplatin induced apoptosis and cell death detected by Tunel and clonogenic assay, respectively. In contrast, over expression of TXNL1 in BGC823/DDP and SGC7901/DDP cells lead to higher cisplatin induced apoptosis and cell death. Moreover, our results demonstrated that the mechanism of TXNL1 regulating cisplatin-induced apoptosis was closely associated with Bcl-2 mediated mitochondria apoptosis pathway. In conclusion, these findings suggest that TXNL1 was a feasible modulator and potential chemotherapeutic target for the cisplatin resistant phenotype of human gastric cancer cells.