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《Anatomy Research》 2018-03
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Mechanism of oncolytic herpes simplex virus G47Δ regulating HER2 in apoptosis of human breast cancer MCF-7 cells

MA Wei;ZHANG Shu-qin;HE Hao;MA Rui;FENG Xiao-min;Department of Oncology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology;  
Objective To investigate the mechanism of HER2-induced apoptosis in human breast cancer MCF-7 cells by oncolytic herpes simplex virus G47Δ. Methods The breast cancer MCF-7/HER2 overexpression group(ER+,HER2-high)and MCF-7/HER2 low expression group were treated with different titer of G47Δ(MOI=0.00,MOI=0.01,MOI=0.1,HER2-low and MCF-7 control(ER+)cells,CCK-8 method test cell survival rate;Flow cytometry was used to detect the apoptosis rate. Hoechst33258 staining was used to detect the morphological changes of breast cancer cells. Western blot was used to detect the expression of HER2 and Cleaved-caspase-3 apoptotic proteins in breast cancer cells after oncolytic herpes simplex virus G47Δ. Results The survival rate of MCF-7/HER2 overexpression group,MCF-7/HER2 low expression group and MCF-7 control group were significantly decreased as the dose of oncolytic herpes simplex virus G47Δ was increased. The rates of HER2 and Cleaved-caspase-3 apoptosis were significantly increased,the difference was statistically significant(P 0.05). The survival rate of MCF-7/HER2 low expression group was significantly higher than that of MCF-7 control group treated with virus G47ΔMOI=0.01,apoptosis rate was significantly decreased,HER2 and Cleaved-caspase-3 apoptotic protein expression decreased significantly;The survival rate of MCF-7/HER2 overexpression group was significantly decreased,the apoptosis rate was significantly increased,HER2 and Cleaved-caspase-3 apoptotic protein expression increased significantly;The survival rate of MCF-7/HER2 low expression group was significantly higher than that of MCF-7 control group treated with G47ΔMOI=0.1,apoptosis rate was significantly decreased,HER2 and Cleaved-caspase-3 apop-totic protein expression decreased significantly;The survival rate of MCF-7/HER2 overexpression group was significantlydecreased,the apoptosis rate was significantly increased,The protein expressions of HER2 and Cleaved-caspase-3 were signifi-cantly increased,with statistical significance(P0.05). Conclusion The oncolytic herpes simplex virus G47Δ effectivelyinduces apoptosis in HER2 overexpressing breast cancer MCF-7 cells. Oncolytic herpes simplex virus G47Δ can promote thedegradation of HER2 protein in a concentration-dependent manner and induce the apoptosis of breast cancer MCF-7 cells.
【Fund】: 湖北省自然科学基金(ZRMS2016000371)
【CateGory Index】: R737.9
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