Fan Bo, Zhang Xiaoyu, Ma Yongliang, Zhang Aili
Cell Physiol Biochem. 2017;43(3):1003-1011. doi: 10.1159/000481698. Epub 2017 Oct 2.
BACKGROUND/AIMS: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer.
We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an up-regulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy.
Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.
背景/目的：粉防己碱和防己诺林碱（Fcn）是从粉防己中提取的两种天然产物。粉防己碱是一种已知的抗膀胱癌化合物，但Fcn对膀胱癌的影响此前尚不清楚。在本研究中，我们重点关注Fcn对膀胱癌的抗肿瘤作用。
我们在体外使用Fcn处理T24和5637膀胱癌细胞系。我们观察到Fcn以浓度依赖性方式抑制膀胱癌细胞的活力。增殖生物标志物PCNA的表达下调。Fcn处理诱导膀胱癌细胞发生凋亡和自噬，表现为caspase-3切割增加、LC3-II/LC3-I比值上调以及p62水平下调。用3-甲基腺嘌呤（3-MA）阻断自噬增强了Fcn诱导的凋亡，表明Fcn诱导的自噬具有适应性。此外，我们观察到Fcn处理抑制mTOR并降低细胞内ATP水平。外源性添加丙酮酸钠（MP）以补偿代谢底物可减轻Fcn诱导的凋亡和自噬。
我们的数据表明，Fcn导致能量生成受损，从而导致膀胱癌细胞发生凋亡和适应性自噬。这些结果表明，Fcn可能是预防和治疗膀胱癌的潜在候选药物。
