Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway
Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway
复制标题
穿心莲内酯抑制自噬通过激活 Akt/mTOR 通路使顺铂耐药的非小细胞肺癌细胞重新敏感
DOI：
10.1016/j.taap.2016.09.009
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发表时间：
2016-11-01
影响因子：
3.8
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Mi, Shanwei;Xiang, Gang;Xu, Qiang
顺铂耐药是影响非小细胞肺癌治疗成功的主要障碍。顺铂耐药的机制尚不完全清楚。在本研究中，我们发现基础自噬的增加伴随着顺铂耐药的发展。同时，Akt/mTOR通路在此过程中发生阻断。在耐药的非小细胞肺癌细胞中，顺铂治疗可诱导该途径的抑制。穿心术内酯是一种天然二萜，通过下调PTEN促进Akt/mTOR信号的激活，抑制自噬，从而使耐药细胞对顺铂介导的凋亡重新敏感。顺铂联合穿心莲内酯治疗可显著抑制体内耐药细胞的生长。这些结果强调了自噬参与顺铂耐药的发展，并表明通过调节Akt/mTOR信号抑制自噬可能是治疗顺铂耐药非小细胞肺癌的一种有希望的策略。(C) 2016 Elsevier Inc.版权所有。
Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. (C) 2016 Elsevier Inc. All rights reserved.