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lüll mda-7/IL-24 induces apoptosis in human HepG2 hepatoma cells by endoplasmic reticulum stress Zhang X; Kang X; Shi L; Li J; Xu W; Qian H; Wu M; Yin ZOncol Rep 2008[Aug]; 20 (2): 437-42mda-7/IL-24 shows tumor-suppressor activity in a broad spectrum of human cancer cells. However, the molecular mechanism by which mda-7/IL-24 induces apoptosis is not well understood and most likely involves different pathways depending on the tumor. We examined the apoptotic effect of the adenovirus-mediated mda-7/IL-24 (Ad.mda-7) on human HepG2 hepatoma cells. We found that blocking the endoplasmic reticulum (ER) stress inhibited apoptosis induced by Ad.mda-7 and down-regulated the expression of caspase-12, Bax and caspase-3. The treatment of subcutaneous tumor xenografts of HepG2 cells with Ad.mda-7 inhibited tumor growth and angiogenesis. As in the in vitro studies, we found that blocking ER stress prevented Ad.mda-7 from inducing apoptosis in liver cancer cells in vivo. Our studies suggest that Ad.mda-7 induces apoptosis of HepG2 cells mainly through activation of the ER stress pathway.|*Apoptosis[MESH]|*Genetic Therapy[MESH]|Adenoviridae/genetics[MESH]|Animals[MESH]|Blotting, Western[MESH]|Carcinoma, Hepatocellular/metabolism/*pathology[MESH]|Caspase 12/metabolism[MESH]|Caspase 3/metabolism[MESH]|Cell Differentiation[MESH]|Cell Proliferation[MESH]|Endoplasmic Reticulum/genetics/*metabolism[MESH]|Flow Cytometry[MESH]|Humans[MESH]|Interleukins/*physiology[MESH]|Liver Neoplasms, Experimental/metabolism/*pathology[MESH]|Mice[MESH]|Mice, Inbred BALB C[MESH]|Mice, Nude[MESH]|Neovascularization, Pathologic/prevention & control[MESH]|Plasmids[MESH]|bcl-2-Associated X Protein/metabolism[MESH] |