期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 67, 期 1, 页码 88-95出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2012.10.016
关键词
ApoG2; Small-molecule inhibitor; Gastric cancer
资金
- Program of the National Basic Research and Development Program of China (973) [2011CB707702]
- National Natural Science Foundation of China [81090272, 81090273, 81101100]
- Natural Science Basic Research Plan in Shaanxi Province of China [2012JQ4015]
- National Key Technology Support Program [2012BAI23B06]
- Fundamental Research Funds for the Central Universities
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. (C) 2012 Elsevier Masson SAS. All rights reserved.
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