School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi, China.
Biomed Pharmacother. 2013 Feb;67(1):88-95. doi: 10.1016/j.biopha.2012.10.016. Epub 2012 Nov 19.
Gastric cancer is one of the most common types of malignancies and proteins from the Bcl-2 family are highly expressed in human gastric cancer. Apogossypolone (ApoG2), the most potent gossypol derivative, has been defined as a novel small-molecule inhibitor of anti-apoptotic Bcl-2 family proteins. However, whether or not it can inhibit the growth and proliferation of gastric cancer cell lines has not been demonstrated to date. Here, we assessed the effects of anti-growth of ApoG2 on gastric cancer cell lines in vitro and explored the possible molecular mechanisms of ApoG2. Using the MTT assay and flow cytometry, we found that ApoG2 has the significant anti-growth effect on MKN28, MKN45 and AGS cell lines in a time- and dose-dependent manner. Compared to (-)-gossypol, MTT assay and flow cytometry results showed that anti-growth effect of ApoG2 is inferior, but the colony formation ability of ApoG2 is superior. Furthermore, western blot results revealed that ApoG2 inhibits the growth and proliferation of gastric cancer cells by down-regulating of Bcl-2 protein expression, up-regulating of Bax and activating of Caspase-3. Taken together, albeit the ApoG2 inferior to (-)-gossypol in many ways on gastric cancer in vitro, our results suggest that ApoG2 could effectively inhibit the growth and proliferation of gastric cancer cell lines through the mitochondrial pathway of apoptosis.
胃癌是最常见的恶性肿瘤之一，Bcl-2 家族蛋白在人类胃癌中高度表达。阿朴戈索酮（ApoG2）是棉酚的最有效衍生物，已被定义为抗凋亡 Bcl-2 家族蛋白的新型小分子抑制剂。然而，迄今为止，尚未证明它是否能抑制胃癌细胞系的生长和增殖。在这里，我们评估了 ApoG2 对体外胃癌细胞系生长的抑制作用，并探讨了 ApoG2 的可能分子机制。通过 MTT 测定和流式细胞术，我们发现 ApoG2 对 MKN28、MKN45 和 AGS 细胞系具有显著的时间和剂量依赖性的生长抑制作用。与 (-)-棉酚相比，MTT 测定和流式细胞术结果表明，ApoG2 的生长抑制作用较弱，但 ApoG2 的集落形成能力较强。此外，Western blot 结果表明，ApoG2 通过下调 Bcl-2 蛋白表达、上调 Bax 和激活 Caspase-3 来抑制胃癌细胞的生长和增殖。总之，尽管 ApoG2 在许多方面对体外胃癌的作用逊于 (-)-棉酚，但我们的结果表明，ApoG2 可以通过细胞凋亡的线粒体途径有效抑制胃癌细胞系的生长和增殖。
