tailieunhanh - Báo cáo khoa học: Vitamin D stimulates apoptosis in gastric cancer cells in synergy with trichostatin A ⁄sodium butyrate-induced and 5-aza-2¢-deoxycytidine-induced PTEN upregulation

Previous studies have shown an anticancer effect of vitamin D, but the mechanisms underlying this action have not been fully explored. Here we show that 1,25-dihydroxyvitamin D3 (VD3, the active form of vitamin D) significantly promoted apoptosis in the undifferentiated gastric cancer cell line HGC-27, and this was accompanied by a concurrent increase in phos-phatase and tensin homolog deleted on chromosome 10 (PTEN) expression on VD3 treatment. | ỊFEBS Journal Vitamin D stimulates apoptosis in gastric cancer cells in synergy with trichostatin A sodium butyrate-induced and 5-aza-2 -deoxycytidine-induced PTEN upregulation Lina Pan1 z Ammar F. Matloob1 Juan Du2 Hong Pan1 Zhixiong Dong2 Jing Zhao2 Yu Feng1 Yun Zhong1 Baiqu Huang2 and Jun Lu1 1 The Institute of Genetics and Cytology Northeast Normal university Changchun China 2 The Key Laboratory of Molecular Epigenetics of Ministry of Education MOE Northeast NormalUniversity Changchun China Keywords I 25-dihydroxyvitamin D3 5-aza-2 -deoxycytidine gastric cancer PTEN trichostatin A sodium butyrate Correspondence J. Lu Institute of Genetics and Cytology Northeast NormalUniversity 5268 Renmin Street Changchun 130024 China Fax 86 431 85099768 Tel 86 431 85098729 E-mail luj809@ These authors contributed equally to this work Received 8 June 2009 revised 22 October 2009 accepted 8 December 2009 doi Previous studies have shown an anticancer effect of vitamin D but the mechanisms underlying this action have not been fully explored. Here we show that 1 25-dihydroxyvitamin D3 VD3 the active form of vitamin D significantly promoted apoptosis in the undifferentiated gastric cancer cell line HGC-27 and this was accompanied by a concurrent increase in phosphatase and tensin homolog deleted on chromosome 10 PTEN expression on VD3 treatment. In contrast knockdown of PTEN expression by stable transfection of PTEN small interfering RNA greatly decreased the apoptosis rate. We further demonstrated that VD3 induced PTEN expression through vitamin D receptor. In addition our evidence showed that vitamin D receptor Egr-1 and p300 induced PTEN expression in a synergistic fashion. Furthermore we found that the histone deacetylase inhibitors trichostatin A and sodium butyrate and the methylation inhibitor 5-aza-2 -deoxycytidine played important roles in vitamin D-induced apoptosis through PTEN upregulation. The data presented in this article .