Up‐regulation of survivin by AKT and hypoxia‐inducible factor 1α contributes to cisplatin resistance in gastric cancer

• DOI: 10.1111/febs.12577
• Publication Date: 2013-10-24T16:51:53Z
• Authors: Xue‐Pu Sun; Xuesong Dong; Lele Lin; Xian Jiang; Zheng Wei; Bo Zhai; Bo Sun; Qiang Zhang; Xiaolong Wang; Hongchi Jiang; Geoffrey W. Kriss...; Haiquan Qiao; Xueying Sun
• Keywords: Survivin; Inhibitor of apoptosis; Hypoxia-Inducible Factors

This study investigated the contribution of survivin and its upstream regulators, AKT hypoxia‐inducible factor 1α ( HIF –1α), to resistance gastric cancer cells cisplatin CDDP ). We found that over‐expression increased SGC 7901 BGC 823 . Its abrogated ‐induced inhibition cell proliferation apoptosis. In contrast, down‐regulation expression using small hairpin RNA (sh ) vectors small‐molecule inhibitor YM 155, or function a recombinant cell‐permeable dominant‐negative protein (d NS ur9), promoted ‐resistant sub‐lines generated from parental by exposure increasing concentrations expressed higher levels –1α in response hypoxia, phosphorylated (p Specific reduced survivin, whereas specific depletion but had no effect on The affected therapeutic efficacy treating tumors mice. enhanced sensitivity HIF‐1α synergized with suppress growth been engineered overexpress survivin. summary, results provide evidence up‐regulation contributes resistance, indicating these pathways may be potential strategy for overcoming treatment cancer.