Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by targeting the PI3K/AKT/mTOR signaling pathway

作者：Liu, Ming; Wang, Jiwei; Qi, Qichao; Huang, Bin; Chen, Anjing; Li, Xingang^*; Wang, Jian

来源：Oncology Reports, 2016, 36(4): 2160-2168.

DOI：10.3892/or.2016.4998

• apoptosis
• glioblastoma
• metabolism
• nitidine chloride
• SC79

Recent studies have demonstrated that nitidine chloride (NC), a natural bioactive alkaloid, displays potent antitumor activity in various types of cancer. In the present study, NC was examined for efficacy in the treatment of human glioblastoma multiforme (GBM) as well as the molecular basis for its more general inhibitory effects in cancer. U251 and U87 GBM cell lines were exposed to three concentrations of NC (5, 25 and 50 mu M) in vitro, and tumor cell growth was assessed on the basis of proliferation, migration and energy metabolism. Decreases in viability and proliferation reached similar to 50% for both cell lines with 50 mu M NC at 24 h as assessed by cell viability Cell Counting Kit-8 (CCK-8) and EdU assays. In wound closure and Transwell assays, migration and invasion were inhibited at 50 mu M after 24 h (similar to 20 and 80%, respectively; P<0.05). ATP and L-lactate levels were also decreased after treatment with NC (50 mu M, 24 h; P<0.05 and P<0.01, respectively). Finally, in western blot analysis, phosphorylation of Akt and mTOR was suppressed by NC, but partially restored when cells were treated simultaneously with a novel Akt activator, SC79. Partial restoration was also observed in viability/proliferation (U251 and U87, similar to 15 vs. 40%; NC vs. NC + SC79; P<0.05) and invasion (U251 and U87, similar to 30 vs. 60%; NC vs. NC + SC79; P<0.05). Our results demonstrated that NC inhibits development of GBM by targeting the PI3K/Akt/mTOR signaling pathway and provides a potential therapeutic agent for the treatment of GBM.

• 出版日期2016-10
• 单位山东大学