mda-7/IL-24 inhibits proliferation and promotes apoptosis of transplanted hepatocellular cancer cells in nude mice
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Abstract:
Objective: To study the proliferation inhibition and apoptosis promotion effect of mda7/IL24 in transplanted hepatocellular cancer cells in nude mice, and to study the related mechanism. Methods: Recombinant vector Ad.mda7 was constructed. BALB/c nude mice liver cancer model was established by subcutaneous implanting of HepG2 cells. Nude mice were administered with Ad.GFP, Ad.mda7 or ALLN+Ad.mda7 via intratumor single point injection. The changes of tumor size and weight were observed. Activation of caspase3, apoptosis of cancer cells, cell proliferationassociated antigen ki67 and microvascular density were assessed by immunohistochemistry and TUNEL method. Caspase12, caspase3 and Bax expression was examined via Western blotting. Results: The tumor sizes of Ad.mda7 treated mice and Ad.GFP treated mice were (312.6±30.24) mm3 vs (520.6±30.00) mm3 (P<0.05), and the weights were (0.321±0.031) g vs (0.534±0.030) g, respectively (P<0.05). Ad.mda7 inhibited expression of ki67 and CD31, and induced activation of caspase3 in subcutaneous tumor xenografts. ALLN reversed the apoptosis inducing effect of Ad.mda7 (P<0.05), downregulated the expression of caspase12, caspase3 and Bax induced by Ad. Mda7. Conclusion: mda7/IL24 can obviously inhibit proliferation and angiogenesis of transplanted hepatocellular cancer cells, and induce apoptosis of hepatocellular cancer cells through activating the endoplasmic reticulum stress pathway.
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Supported by the National Natural Science Foundation of China (No.30873020)