Abstract:Objective: To investigate the mechanism for the selective killing effect of oncolyic adenovirus SG600-IL24 bearing human mda-7/IL-24 on l hepatocullular carcinoma (HCC) cells.
Methods: The oncolytic adenovirus SG600-IL24 carrying human MDA-7/IL-24 (SG600-IL24) was constructed, and then was infected into the HCC cell lines HepG2 and HCCLM3 and normal liver cell line L02, respectively. In each cell line after infection, the changes in gene and protein expressions of STAT3 and its downstream signaling molecules as well as the protein expression of phosphorylated STAT3 were determined by RT-PCR and Western blot, respectively.
Results: The oncolytic adenovirus SG600-IL24 carrying human mda-7/IL-24 was constructed successfully. After SG600-IL24 infection, the expressions of human mda-7/IL-24 gene and protein were significantly increased in all the cell lines (all P<0.05). In the two types of HCC cells, the STAT3 expression level was significantly downregulated, and its downstream signaling molecule c-myc, Bcl-xl, Bcl-2, cyclin D2, survivin, MMP-2, MMP-9, XIAP, OPN, and VEGF were downregulated while Bax were upregulated significantly, and all presented with a time-dependent trend (all P<0.05); the protein expression of p-STAT3 was increased after infection and reached to a peak in 2 hours, and then decreased. No significant changes were noted in expressions of STAT3 and its downstream molecules in L02 cells after infection (all P>0.05).
Conclusion: The mechanism for the selective killing effect of oncolyic adenovirus SG600-IL24 bearing human mda-7/IL-24 on HCC cells may probably be associated with its selectively inhibiting STAT3 signaling pathway in HCC cells, with no influence on normal liver cells.