Research Papers:
Tripchlorolide induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR pathway and improves cisplatin sensitivity in A549/DDP cells
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Abstract
Li-Min Chen1,2,3, Tian-Jiao Song1,2,3, Jian-Hong Xiao4, Zheng-Hui Huang1, Yong Li1 and Ting-Yan Lin1
1Department of Respiratory Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, People’s Republic of China
2Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, People’s Republic of China
3Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, People’s Republic of China
4Department of Respiratory Medicine, Mindong Hospital of Ningde City, Fu’an, Fujian 355000, People’s Republic of China
Correspondence to:
Li-Min Chen, email: [email protected]
Ting-Yan Lin, email: [email protected]
Keywords: tripchlorolide, autophagy, lung cancer, PI3K/AKT/mTOR, MDR1
Received: November 04, 2016 Accepted: June 20, 2017 Published: July 12, 2017
ABSTRACT
Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT. Expression of LC3II increased in parallel to the increase of the T4 concentration in both A549 and A549/DDP cells and was repressed by overexpression of AKT. The expression levels of PI3-K, PI3-P, AKT, TSC2, mTOR, p70S6K and 4E-BP1 were minimally affected by the wortmannin, perifosine, or rapamycin plus T4 treatments, but their phosphorylated products were greatly affected in A549 lung cancer cells and slightly affected in A549/DDP lung cancer cells. These results indicate that T4 induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway. We further found that T4 decreased expression of MDR1 and improved cisplatin sensitivity of A549/DDP cells. Altogether, these results have meaningful implications for tumor therapy in the future.
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PII: 19201