科研之友
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摘要
As the new oral selective VEGFR tyrosine kinase inhibitor, axitinib (AG-013736) exerts powerful antitumor activity in multiple solid tumors, while its' effect was unclear in gastric cancer. We aimed to investigate the antitumor activity of axitinib alone or combined with chemotherapeutic drugs against human gastric cancer cells in vitro and in vivo. The IC50 values of drugs were determined by MTS assay. The median effect of Chou-Talalay was used to assess the synergistic effect of two drugs. Flow cytometry was employed to analyze cell cycle and cell apoptosis. Cell senescence and microvessel density were evaluated by SA-beta-gal staining and CD34 staining, respectively. BGC-823-derived xenografts in nude mice were established to investigate the effects of drugs in vivo. Axitinib alone could inhibit cell proliferation and retard tumor growth through inducing cell cycle arrest at G2/M phase, cell senescence, cell apoptosis, and antiangiogenesis in vitro and in vivo. Axitinib combined with 5-fluorouracil (5-FU) had synergistic inhibitory effect compared to axitinib or 5-FU alone. However, the highest inhibitory effect was found between axitinib and cisplatin (inhibitory ratio > 80 % compared to control), which was significantly higher than any single drug (inhibitory ratio for single 5-FU, cisplatin, and axitinib > 10, > 40, and > 40 %, respectively, compared to control) or axitinib combined with 5-FU (inhibitory ratio > 50 % compared to control). We highlighted for the first time that axitinib alone or in combination with 5-fluorouracil or cisplatin has potent antitumor activity against human gastric cancer in vitro and in vivo, which provided solid evidence for future clinical trial.
- 出版日期2014-9
- 单位北京大学; 浙江省肿瘤医院
