Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China.
Oncol Rep. 2017 Aug;38(2):1051-1058. doi: 10.3892/or.2017.5747. Epub 2017 Jun 22.
The tuber of amorphophallus konjac (TuAK) is an antitumor herb used in traditional Chinese medicine. The present study investigated the inhibitory effect of TuAK against gastric cancer and the underlying mechanisms associated with two programmed cell death pathways, apoptosis and autophagy. TuAK was extracted by organic solvents including ethanol and ligarine. The extract of TuAK, shortened as TuAKe, significantly inhibited the growth of cultured gastric cancer cell lines SGC-7901 and AGS, with IC50 of 35-45 µg/ml. TuAKe could increase cell apoptosis and induce cell cycle arrest. For the apoptosis-associated proteins, expressions of survivin and Bcl-2 were decreased by treatment of TuAKe, and the expression of Bax and caspase-9 was increased. Furthermore, TuAKe could promote autophagy, and the antitumor efficacy of TuAKe was significantly hampered by targeted suppression of autophagy, suggesting that autophagy contributed to TuAKe-induced cell death. Furthermore, patients with gastric cancer who received TuAK-based medicinal decoction achieved improved scores in assessment of life quality compared with those without TuAK treatment. This study demonstrated the antitumor activity of TuAKe against gastric cancer, and is the first report to show that the underlying mechanism is associated with induction of autophagy. Our data provided support of the clinical use of amorphophallus konjac-based medication in combination with classical chemotherapy to achieve optimized outcome for gastric cancer.
魔芋根茎(TuAK)是一种传统中药中的抗肿瘤草药。本研究探讨了 TuAK 对胃癌的抑制作用及其与两种程序性细胞死亡途径(凋亡和自噬)相关的潜在机制。TuAK 通过包括乙醇和液体石蜡在内的有机溶剂进行提取。TuAK 的提取物,简称 TuAKe,显著抑制培养的胃癌细胞系 SGC-7901 和 AGS 的生长,IC50 为 35-45μg/ml。TuAKe 可增加细胞凋亡并诱导细胞周期停滞。对于与凋亡相关的蛋白, Survivin 和 Bcl-2 的表达被 TuAKe 处理下调,而 Bax 和 caspase-9 的表达增加。此外,TuAKe 可促进自噬,而自噬的靶向抑制显著阻碍了 TuAKe 诱导的细胞死亡,表明自噬有助于 TuAKe 诱导的细胞死亡。此外,接受基于魔芋根茎的药物治疗的胃癌患者在生活质量评估中得分得到改善,与未接受 TuAK 治疗的患者相比。本研究证明了 TuAKe 对胃癌的抗肿瘤活性,并且是第一个表明潜在机制与诱导自噬相关的报告。我们的数据为魔芋根茎为基础的药物与经典化疗相结合在胃癌中的临床应用提供了支持,以实现优化的结果。