Antitumor Mechanism of Survivin Mediated Conditionally Replicative Oncolytic Adenoviruse Expressing IL-24 in Human Hepatocellular Carcinoma Cell Line PLC

Hai Jiang¹, Xin-Xin Ding², Hong Liu³, Hong-Xia Xie¹, Kang-Jian Zhang^1*

¹Xin Yuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University,Hangzhou 310018, China; ²Institue of Biochemistry, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Chi

Abstract: Antitumor mechanism in human hepatocellular carcinoma cell line PLC induced by conditionally replicative oncolytic adenoviruse (Ad.sp-E1A(Δ24)-IL-24) is not clear. PLC was treated with PBS， Ad.sp-E1A(Δ24) or Ad.sp-E1A(Δ24)-IL-24 for 48 h， respectively. The cell cycle was detected by flow cytometry(FCM). Western blot detected the changes of apoptosis-related protein expression. FCM confirmed that both Ad.sp-E1A(Δ24) and Ad.sp-E1A(Δ24)-IL-24 can block PLC cells in S phase， of which the percentages were 43.74%±6.61% and 49.48%±7.60%compared with 18.91%±1.83% of control (P<0.05). Western blot indicated both Ad.sp-E1A(Δ24) and Ad.sp-E1A(Δ24)-IL-24 can increase the expression of CHOP， cleavaged caspase 12， p-STAT3 and p-p38 MAPK. Obviously， the virus Ad.sp-E1A(Δ24)-IL-24 had the stronger ability of inducing the above proteins， but both of the viruses had no effect on inducing expression of SOCS3. In conclusion， the recombinant oncolytic adenovirus blocked PLC cells in S phase effectively， and induced apoptosis of PLC cells directly related to endoplasmic reticulum stress， STAT3 and MAPK
pathways.

CSTR: 32200.14.cjcb.2010.05.0010