Anti-Hepatocarcinoma Effect of P28 Promoter-Driven Oncolytic Adenovirus Carrying TRAIL Gene
JIN Xiaoting1,2, LIU Xinyuan1,2,3, CHEN Ruoyu3*, LI Ning3*, ZHANG Kangjian2,3,4*
P28 (also known as PSMD10, P28GANK or gankyrin) is highly expressed (96.9%) in HCC (hepatocarcinoma) but not in normal cells. Therefore, P28 promoter was used to design a novel oncolytic virus vector with liver cancer targeting. On this basis, OncoAd-P28-E1A-ΔE1B-TRAIL, a novel oncolytic adenovirus carrying TRAIL (TNF related apoptosis inducing ligand gene) was designed for HCC therapy. The infection of HCC cells with OncoAd-P28-TRAIL showed that TRAIL protein could be highly expressed in hepatoma cells. Crystal violet staining showed that the virus could selectively target hepatoma cells and had no obvious toxicity to normal human hepatocytes at 10 MOI. In vitro level killing and apoptosis studies showed that OncoAd-P28-TRAIL inhibited both Huh-7 and Hep-3B hepatoma cells in a time- and dose-dependent manner, and could significantly promote apoptosis of HCC cells. In vivo, the nude mice HCC-CDX therapy showed that the oncolytic adenovirus could promote the apoptosis of tumor cells and infiltration of immune cells, thus significantly inhibiting the growth of subcutaneous tumor of HCC cells. These results fully indicate that OncoAd-P28-TRAIL can effectively inhibit the development of HCC and is a potential candidate drug for the treatment of HCC.
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