摘要
顺铂是一种在胃癌治疗中最常用的药物。然而,耐药性是有效治疗的重大障碍并源于多种机制,如增强DNA修复和抗细胞凋亡。我们的前期研究结果表明XRCC1是顺铂诱导DNA损伤和细胞凋亡的一种关键调控因子。TXNL1,硫氧还蛋白家族的一员,通过泛素-蛋白酶体途径负向调节XRCC1的表达。在此,我们研究了在顺铂引起的细胞凋亡中TXNL1的作用。我们的数据表明在顺铂耐药性胃癌细胞株BGC823/DDP和SGC7901/DDP细胞明显低于顺铂敏感细胞株BGC823和SGC7901。在BGC823和SGC7901中TXNL1表达的抑制导致分别由末位标记法和成株试验检测的顺铂诱导的细胞凋亡和死亡的耐药性增加。相反,在BGC823/DDP 和 SGC7901/DDP中TXNL1的过度表达导致顺铂诱导的细胞凋亡和死亡更高。另外,我们的研究结果表明TXNL1调节顺铂诱导的细胞凋亡的机制与Bcl-2介导的线粒体细胞凋亡途径有密切关系。总之,这些结果表明TXNL1对于顺铂耐药性的人胃癌细胞表型是可行的调控因子和潜在的化学治疗靶标。
关键词: 细胞凋亡,Bcl-2,顺铂,胃癌,TXNL1,XRCC1。
图形摘要
Current Cancer Drug Targets
Title:TXNL1 Induces Apoptosis in Cisplatin Resistant Human Gastric Cancer Cell Lines
Volume: 14 Issue: 9
Author(s): Pan Ni, Wenxia Xu, Yajie Zhang, Qi Chen, Aiping Li, Shouyu Wang, Shan Xu and Jianwei Zhou
Affiliation:
关键词: 细胞凋亡,Bcl-2,顺铂,胃癌,TXNL1,XRCC1。
摘要: 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.
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Cite this article as:
Pan Ni, Wenxia Xu, Yajie Zhang, Qi Chen, Aiping Li, Shouyu Wang, Shan Xu and Jianwei Zhou , TXNL1 Induces Apoptosis in Cisplatin Resistant Human Gastric Cancer Cell Lines, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141028094612
DOI https://dx.doi.org/10.2174/1568009614666141028094612 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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