Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, Changhua, Taiwan, ROC Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan, ROC Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan, ROC School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
Anticancer Res. 2014 Dec;34(12):7097-110.
Tanshinone IIA (Tan-IIA) is extracted from Danshen (Salviae miltiorrhizae radix). It possesses antitumor activity against a variety of human cancer cells and its induction of apoptosis and inhibition of proliferation of gastric cancer cells are well-documented. However, the molecular mechanisms by which Tan-IIA inhibits gastric cancer have not been well-elucidated. In the present study, we evaluated the cytotoxicity of Tan-IIA against human gastric cancer AGS cells by the (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) MTT assay. The protein expression of tumor necrosis factor-alpha (TNF-α), FAS, p53, p21, cyclin A, cyclin B1, extracellular-related kinase (ERK), phospho extracellular-related kinase (p-ERK), p38, p-p38, Jun-amino-terminal kinase (JNK), phospho Jun-amino-terminal kinase (p-JNK) and β-actin in AGS cells were measured by western blotting. The cell-cycle distribution was analyzed by flow cytometry. The results showed that Tan-IIA inhibited AGS cells with time- and dose-dependent manners. AGS cells treated with Tan-IIA up-regulated the protein expression of TNFα, FAS, p-p38, p-JNK, p53, p21, caspase-3 and caspase-8 but reduced that of p-ERK, CDC2, cyclin A, and cyclin B1. The results also showed that Tan-IIA dose dependently induced G2/M phase arrest. These findings demonstrate that Tan-IIA can inhibit AGS human gastric cancer cells; one of the molecular mechanisms may be through increasing the protein expression of p-p38 and p-JNK, but decreasing that of p-ERK to induce the activation of p53, followed by increasing the protein expression of p21 to down-regulate CDC2 and cyclin B1 expression which then induces G2/M phase arrest. Another route may be through increasing the protein expression of TNF-α, FAS, caspase-8 and caspase-3 to induce apoptosis.
丹参酮 IIA（Tan-IIA）从丹参（Salviae miltiorrhizae radix）中提取。它具有抗多种人类癌细胞的抗肿瘤活性，其诱导胃癌细胞凋亡和抑制增殖的作用已有详细记录。然而，Tan-IIA 抑制胃癌的分子机制尚未得到很好的阐明。在本研究中，我们通过（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）MTT 测定法评估了 Tan-IIA 对人胃癌 AGS 细胞的细胞毒性。肿瘤坏死因子-α（TNF-α）、FAS、p53、p21、细胞周期蛋白 A、细胞周期蛋白 B1、细胞外相关激酶（ERK）、磷酸化细胞外相关激酶（p-ERK）、p38、p-p38、Jun-氨基末端激酶（JNK）、磷酸化 Jun-氨基末端激酶（p-JNK）和β-肌动蛋白在 AGS 细胞中的蛋白表达通过 Western blot 进行测量。通过流式细胞术分析细胞周期分布。结果表明，Tan-IIA 以时间和剂量依赖性方式抑制 AGS 细胞。用 Tan-IIA 处理的 AGS 细胞上调了 TNFα、FAS、p-p38、p-JNK、p53、p21、caspase-3 和 caspase-8 的蛋白表达，但降低了 p-ERK、CDC2、细胞周期蛋白 A 和细胞周期蛋白 B1 的蛋白表达。结果还表明，Tan-IIA 剂量依赖性地诱导 G2/M 期阻滞。这些发现表明 Tan-IIA 可以抑制 AGS 人胃癌细胞；其中一种分子机制可能是通过增加 p-p38 和 p-JNK 的蛋白表达，降低 p-ERK 的蛋白表达来诱导 p53 的激活，随后增加 p21 的蛋白表达下调 CDC2 和细胞周期蛋白 B1 的表达，从而诱导 G2/M 期阻滞。另一种途径可能是通过增加 TNF-α、FAS、caspase-8 和 caspase-3 的蛋白表达来诱导细胞凋亡。
