Enhanced anticancer effect of the combination of cisplatin and TRAIL in triple-negative breast tumor cells.
Enhanced anticancer effect of the combination of cisplatin and TRAIL in triple-negative breast tumor cells.
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DOI：
10.1158/1535-7163.mct-10-0571
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发表时间：
2011-03
影响因子：
5.7
通讯作者：
Reddy KB
中科院分区：
文献类型：
--
作者：
Xu L;Yin S;Banerjee S;Sarkar F;Reddy KB
与其他乳腺癌亚型相比，三阴性乳腺癌(TNBC)患者的预后较差。激素或基于赫赛汀的治疗被发现是无效的，因为靶受体如ER、PR和HER-2扩增的丢失。传统的化疗和/或放射治疗对TNBC患者的疗效似乎也有限。我们在体外研究了顺铂联合TRAIL对一个正常和两个TNBC细胞的作用。体外研究表明，与正常乳腺细胞系CRL8799相比，顺铂联合TRAIL可显著增加TNBC细胞系CRL2335和MDA-MB-468的细胞死亡率约60-70%。顺铂/TRAIL可抑制TNBC细胞中EGFR、p63、Survivin、Bcl2和Bclxl的表达。SiRNA对TNBC细胞EGFR和/或p63蛋白的特异性抑制不会增加TRAIL诱导的细胞凋亡。然而，siRNA抑制Survivin可增强TRAIL诱导的细胞凋亡。这些结果提示Survivin可能在顺铂加TRAIL诱导的TNBC细胞凋亡中起重要作用。在体内实验中，与未治疗的对照肿瘤相比，顺铂联合TRAIL治疗的小鼠对CRL2335异种移植瘤有显著的抑制作用。综上所述，这些数据表明顺铂联合TRAIL治疗有可能为改善TNBC患者的治疗结果提供一种新的策略。
Women with triple negative breast cancer (TNBC) have a worse prognosis compared with other breast cancer subtypes. Hormonal or Herceptin-based therapies were found to be ineffective because of the loss of target receptors such as ER, PR and HER-2 amplification. Conventional chemo- and/ or radiation therapy also seems to have limited efficacy in TNBC patients. We studied the effects of cisplatin plus TRAIL on one normal and two TNBC cells in vitro. The in vitro studies indicate that cisplatin plus TRAIL significantly enhanced cell death in TNBC cell lines CRL2335 and MDA-MB-468 by ~60–70% compared to ~ 10–15% in CRL8799 normal breast cell line. Treatment with cisplatin/TRAIL also inhibited the expression of EGFR, p63, survivin, Bcl-2 and Bcl-xL in TNBC cells. Specific inhibition of EGFR and/or p63 protein in TNBC cells by siRNA does not increase TRAIL-induced apoptosis. However, inhibition of survivin by siRNA enhances TRAIL-induced apoptosis. These observations suggested the possibility that Survivin played an important role in cisplatin plus TRAIL-induced apoptosis in TNBC cells. In vivo experiments, treatment of mice with cisplatin plus TRAIL resulted in a significant inhibition of CRL2335 xenograft tumors compared to untreated control tumors. Taken together the data suggests that cisplatin plus TRAIL treatment have the potential of providing a new strategy for improving the therapeutic outcome in TNBC patients.