标题：Gambogic acid improves non-small cell lung cancer progression by inhibition of mTOR signaling pathway
作者：Zhao, Teng; Wang, Hong-Jian; Zhao, Wen-Wen; Sun, Yi-Ling; Hu, Li-Kuan
作者机构：[Zhao, Teng; Hu, Li-Kuan] Shandong Univ, Qilu Hosp, Dept Oncol, 107 West Cultural Rd, Jinan 250012, Shandong, Peoples R China.; [Wang, Hong-Jian; Su 更多
通讯作者地址：[Hu, LK]Shandong Univ, Qilu Hosp, Dept Oncol, 107 West Cultural Rd, Jinan 250012, Shandong, Peoples R China.
来源：KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
关键词：Gambogic acid; Autophagy; Multidrug resistance; Cell death
摘要：Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce apoptosis, and enhance reactive oxygen species accumulation. However, whether GA could improve multidrug resistance through modulating autophagy has never been explored. We demonstrated that the combination of GA and cisplatin (CDDP) resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using the MTT assay. Furthermore, treatment with GA significantly increased autophagy in these cells. More importantly, GA-induced cell death could be largely abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting that GA-induced cell death was dependent on autophagy. Western blot analysis showed that GA treatment suppressed the activation of Akt, mTOR, and S6. In addition, using a GA and rapamycin combination induced more cell death compared to either GA or rapamycin alone. In summary, GA may have utility as an adjunct therapy for non-small cell lung cancer (NSCLC) patients through autophagy-dependent cell death, even when cancer cells have developed resistance to apoptosis. Copyright (C) 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license.