Inhibitory Effect of Recombinant Oncolytic Herpes Simplex Virus on the Transplanted Tumor of Colon Cancer in Mice

To study the inhibitory effect of the recombinant oncolytic herpes simplex virus (oHSV) MH1004 and MH1006 expressing p53 and IL-12 genes on the transplanted colon cancer tumors in mice. Western blot and ELISA were used to detect the expression of therapeutic gene p53 and IL-12 in the cells infected with MH1004 and MH1006 respectively; Colon cancer cell CT26 was used to construct the subcutaneous transplanted tumor model in mice. HSV-wt, HSV empty viral vector MH1001 and MH1005, as well as oHSV MH1004 and MH1006 were injected into the tumor to observe the effect of the oHSVs on tumor growth, survival rate and tumor size in the mice. The results were shown as below, p53 protein was detected by Western blot in the cells infected with MH1004, and IL-12 protein was detected by ELISA in the cells infected with MH1006 in the early stage. At day 21 of treatment for tumor bearing mice, the tumor volumes of MH1004, MH1005 and MH1006 treatment groups were 2 820.69±2 539.35 mm³, 2 127.31±2 017.02 mm³ and 1 414.36±1 639.19 mm³ respectively, which were all significantly smaller than that of Mock group (7 682.92±2 648.74 mm³)(P<0.01). At day 42 of the treatment, the tumor in one of the mice from MH1004, MH1005 and MH1006 groups all disappeared respectively, and the survival rates of mice of MH1004(100%) and MH1006 (100%) groups were significantly higher than that of MH1001(66.67%), MH1005(66.67%), HSV-wt (50%) and Mock (50%) groups (P<0.05). This study suggests MH1005 is an ideal replication oncolytic viral vector; oHSV expressing p53 and IL-12 can effectively inhibit the growth of colon cancer tumors in mice, which is a potential new method for colon cancer treatment.