Antitumor effect of imperatorin enhances cytotoxicity of doxorubicin to HeLa cells / 中国病理生理杂志

ABSTRACT

AIM:To determine whether imperatorin would enhance the effect of doxorubicin therapy on cervi -cal cancer in vitro.METHODS:The viability of HeLa cells treated with imperatorin and doxorubicin was determined by MTT assay in vitro.The expression of Bcl-2 protein family ( Mcl-1, Bcl-2, Bcl-xL, Bad and Bax ) in HeLa cells treated with imperatorin and doxorubicin was evaluated by Western blot analysis .The apoptosis and mitochondrial membrane poten-tial (ΔΨm ) in the HeLa cells treated with imperatorin and doxorubicin were analyzed by flow cytometry .A Mcl-1 expres-sion vector was constructed , and its role in the cytotoxicity of imperatorin plus doxorubicin to HeLa cells was detected by MTT assay.RESULTS: Addition of imperatorin significantly enhanced the cytotoxicity of doxorubicin to HeLa cells in vitro.Mcl-1 expression was down-regulated by imperatorin but was not influenced by doxorubicin in the HeLa cells .A com-bination of imperatorin and doxorubicin induced apoptosis and ΔΨm collapse more significantly compared with the treatment with imperatorin or doxorubicin alone .Furthermore, the imperatorin-induced sensitization for doxorubicin cytotoxicity to HeLa cells was abolished by the transfection with Mcl-1 expression plasmid .CONCLUSION:The combination of doxoru-bicin with imperatorin enhances the antitumor effect of doxorubicin on cervical cancer cells via targeting Mcl -1.