Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
J Ethnopharmacol. 2012 Jun 1;141(2):635-41. doi: 10.1016/j.jep.2011.08.010. Epub 2011 Aug 12.
We had reported that Astragalus saponins (AST) exert promising anti-tumorigenic effects by suppressing the growth of HT-29 human colon cancer cells and tumor xenograft. In the present study, we further investigated the anti-angiogenic property of AST in human gastric adenocarcinoma cells (AGS) and attempted to elucidate the underlying mechanism.
Viability of AGS cells was measured by using the MTT reduction method. Western blotting was performed to examine the effect of AST on apoptotic- and cell growth-related protein expression. Effect of AST on cell cycle progression was also evaluated using PI staining. A Matrigel invasion assay was then employed to demonstrate the effect of AST on the invasiveness of gastric cancer cells. The expression of invasion-associated proteins (VEGF and MMPs) was also investigated.
AST could induce apoptosis in AGS cells by activating caspase 3 with subsequent cleavage of poly(ADP-ribose) polymerase. Besides, cell cycle arrest at the G2/M phase had been observed in AST-treated cells, leading to substantial growth inhibition. The anti-proliferative effect of AST was associated with the regulation of cyclin B1, p21 and c-myc. Results indicate that the number of AGS cells invaded through the Matrigel membrane was significantly reduced upon AST treatment, with concomitant down-regulation of the pro-angiogenic protein vascular endothelial growth factor (VEGF) as well as the metastatic proteins metalloproteinase (MMP)-2 and MMP-9.
AST derived from the medicinal plant Astragalus membranaceus could modulate the invasiveness and angiogenesis of AGS cells besides its pro-apoptotic and anti-proliferative activities. These findings also suggest that AST has the potential to be further developed into an effective chemotherapeutic agent in treating advanced and metastatic gastric cancers.
我们曾报道过黄芪皂苷（AST）通过抑制 HT-29 人结肠癌细胞和肿瘤异种移植物的生长，发挥出有前景的抗肿瘤作用。在本研究中，我们进一步研究了 AST 对人胃腺癌（AGS）细胞的抗血管生成特性，并试图阐明其潜在机制。
采用 MTT 还原法测定 AGS 细胞活力。采用 Western blot 法检测 AST 对凋亡和细胞生长相关蛋白表达的影响。还通过 PI 染色评估 AST 对细胞周期进程的影响。然后采用 Matrigel 侵袭实验来证明 AST 对胃癌细胞侵袭性的影响。还研究了侵袭相关蛋白（VEGF 和 MMPs）的表达。
AST 通过激活 caspase 3 及其随后的多聚（ADP-核糖）聚合酶的裂解，可诱导 AGS 细胞凋亡。此外，AST 处理的细胞中观察到细胞周期停滞在 G2/M 期，导致生长受到显著抑制。AST 的抗增殖作用与细胞周期蛋白 B1、p21 和 c-myc 的调节有关。结果表明，AST 处理后，AGS 细胞穿过 Matrigel 膜的侵袭细胞数显著减少，同时下调促血管生成蛋白血管内皮生长因子（VEGF）以及转移性蛋白基质金属蛋白酶（MMP）-2 和 MMP-9。
来源于药用植物黄芪的 AST 除了具有促凋亡和抗增殖活性外，还可以调节 AGS 细胞的侵袭性和血管生成。这些发现还表明，AST 有可能进一步开发为治疗晚期和转移性胃癌的有效化疗药物。
