Department of Radiology, Jilin Province Cancer Hospital, Changchun, China.
Pharmacology. 2017;100(5-6):283-291. doi: 10.1159/000479320. Epub 2017 Aug 19.
Lung cancer is one of the major causes of cancer morbidity and mortality around the world, and the resistance to cisplatin is a critical issue to chemotherapy in lung cancer patients. Transforming growth factor β (TGF-β) signal pathway abnormality is widely observed in drug resistance during lung cancer chemotherapy. Here, we investigated the effects of heat-shock protein 27 (HSP27) in the TGF-β-induced cisplatin resistance in lung cancer cell. In this study, our results indicated that the mRNA and protein expression of HSP27 were significantly increased in human lung cancer tissues. TGF-β induced the mRNA and protein expression of HSP27 in human lung cancer cell (A549). Treatment of TGF-β-induced cisplatin resistance in A549 cell through blocking the cisplatin-induced apoptosis and cell death, which characterized as the increasing of cell viability and decreasing of PARP and caspase3 cleavage in the cisplatin-treated cell. Knockdown of SMAD3 attenuated the TGF-β-induced HSP27 expression and restored the TGF-β-induced cisplatin resistance in A549 cell. Additionally, the knockdown of HSP27 blocked TGF-β-induced cisplatin resistance via decreasing cell viability and increasing cell apoptosis in A549 cell. These data therefore suggested that HSP27 is critical to lung cancer progression and TGF-β-induced cisplatin resistance in human lung cancer cell, and may provide an effective clinical strategy in lung cancer patients with resistance to chemotherapy.
肺癌是全世界癌症发病率和死亡率的主要原因之一，而对顺铂的耐药性是肺癌患者化疗的一个关键问题。转化生长因子β（TGF-β）信号通路异常在肺癌化疗的耐药性中广泛存在。在这里，我们研究了热休克蛋白 27（HSP27）在 TGF-β诱导的肺癌细胞顺铂耐药中的作用。在这项研究中，我们的结果表明 HSP27 的 mRNA 和蛋白表达在人肺癌组织中显著增加。TGF-β诱导人肺癌细胞（A549）中 HSP27 的 mRNA 和蛋白表达。通过阻断顺铂诱导的凋亡和细胞死亡，TGF-β处理可诱导 A549 细胞中的顺铂耐药，其特征为顺铂处理细胞中的细胞活力增加和 PARP 和 caspase3 切割减少。SMAD3 的敲低减弱了 TGF-β诱导的 HSP27 表达，并恢复了 A549 细胞中 TGF-β诱导的顺铂耐药性。此外，HSP27 的敲低通过降低 A549 细胞中的细胞活力和增加细胞凋亡来阻断 TGF-β诱导的顺铂耐药性。因此，这些数据表明 HSP27 对人类肺癌细胞的肺癌进展和 TGF-β诱导的顺铂耐药性至关重要，并可能为化疗耐药的肺癌患者提供有效的临床策略。
