Department of Oncology, Qilu Hospital of Shandong University, Ji'nan City, Shandong Province, PR China.
The Second Department of Oncology, Tengzhou Central People's Hospital, Tengzhou City, Shandong Province, PR China.
Kaohsiung J Med Sci. 2017 Nov;33(11):543-549. doi: 10.1016/j.kjms.2017.06.013. Epub 2017 Jul 25.
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.
藤黄酸（GA）已被证明能抑制癌细胞增殖、诱导细胞凋亡和增加活性氧物质积累。然而，GA 是否能通过调节自噬来改善多药耐药性，这一点尚未被探索。我们通过 MTT 检测证实，GA 与顺铂（CDDP）联合使用对 A549 和 NCI-H460 细胞的生长抑制作用更强。此外，GA 处理显著增加了这些细胞中的自噬。更重要的是，用 3-甲基腺嘌呤（3-MA）或氯喹（CQ）处理可显著抑制 GA 诱导的细胞死亡，表明 GA 诱导的细胞死亡依赖于自噬。Western blot 分析表明，GA 处理抑制了 Akt、mTOR 和 S6 的激活。此外，与单独使用 GA 或雷帕霉素相比，GA 和雷帕霉素联合使用诱导了更多的细胞死亡。综上所述，GA 可能通过自噬依赖性细胞死亡对非小细胞肺癌（NSCLC）患者具有辅助治疗作用，即使癌细胞对细胞凋亡产生了耐药性。
