Open AccessGambogic acid improves non‐small cell lung cancer progression by inhibition of mTOR signaling pathway
Author(s) -
Zhao Teng,
Wang HongJian,
Zhao WenWen,
Sun YiLing,
Hu LiKuan
Publication year - 2017
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2017.06.013
Subject(s) - autophagy , gambogic acid , pi3k/akt/mtor pathway , programmed cell death , apoptosis , medicine , cancer research , cell growth , lung cancer , reactive oxygen species , protein kinase b , cisplatin , cancer cell , microbiology and biotechnology , cancer , biology , biochemistry , oncology , chemotherapy
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.