Targeted blocking STAT3 enhances sensitivity of liver cancer cell H22 to chemo-therapy drug doxorubicin / 中国免疫学杂志

ABSTRACT

Objective:To investigate the theraputic effect of STAT3 Decoy-ODN combined with chemotherapy drugs for HCC commonly used in clinical,include doxorubicin (DOX),5-fluorouracil (5-Fu) and cisplatin;and,analyzing the impact of combination therapy on the immune system.Methods:MTT assay was used to detect cell proliferation,and Annexin-V /7AAD double staining assay was used to detect the apoptosis of Decoy ODN transfected-hepatoma cells treated with chemotherapy drugs.The tumor growth and survival rate of H22 tumor-bearing mice treated with DOX combined with STAT3 Decoy-ODN or not were observed.FACS was applied to analyze the subpopulation and activation of PBMCs from tumor-bearing mice treated as above,and to evaluate the influence of DOX or DOX-treated tumor cells on spleen lymphocyte activation.Results: DOX-induced the suppression and the apoptosis of H22 were significantly increased by Decoy ODN transfection.The combination treatment of Decoy ODN and DOX significantly reduced H22 tumor growth and extended the survival of tumor-bearing mice.Low-dose DOX could increase the proportion of T cells and CD69+T cells in PBMCs,as well as the expression of CD107a and IFN-γin NK cells.DOXt-reated H 22 cells increased the proportion of T cells.Conclusion:Targeted blocking STAT3 could enhance the sensitivity of liver cancer cells to doxorubicin.So,combination therapy may improve DOX therapeutic effect and reduce DOX-mediated side effects.Furthermore,low dose of DOX can promote the activation of host immune system by acting on tumor cells.