Growth arrest‐specific gene 1 is downregulated and inhibits tumor growth in gastric cancer

Gastric cancer is one of the leading causes of malignancy‐related mortality in the world, and malignant growth is a crucial characteristic in gastric cancer. In our previous study, we found that growth arrest‐specific gene 1 (GAS1) suppression was involved in making gastric cancer cells multidrug‐resistant by protecting them from drug‐induced apoptosis. In the present study, we investigated the potential role of GAS1 in the growth and proliferation of gastric cancer. We demonstrated that GAS1 expression was decreased in gastric cancer, and patients without GAS1 expression showed shorter survival times than those with GAS1 expression. Both gain‐of‐function (by overexpression of GAS1) and loss‐of‐function (by GAS1‐specific small interfering RNA knockdown) studies showed that increased GAS1 expression significantly reduced the colony‐forming ability of gastric cancer cells in vitro and reduced cell growth in vivo, whereas decreased GAS1 expression had the opposite effects. Moreover, upregulation of GAS1 induced cell apoptosis, and downregulation of GAS1 inhibited apoptosis. Furthermore, we demonstrated that GAS1 could induce gastric cancer cell apoptosis, at least in part through modulating the Bcl‐2/Bax ratio and the activity of caspase‐3. Taken together, our results strongly indicate that GAS1 expression was decreased in gastric cancer and was predictive of a poor prognosis. Restoration of GAS1 expression inhibited cell growth and promoted apoptosis of gastric cancer cells, at least in part through modulating the Bcl‐2/Bax ratio and activating caspase‐3, suggesting that GAS1 might be used as a novel therapeutic candidate for gastric cancer.

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