The Novel Synergetic Combination Of Isoniazid Along With Doxorubicin Induced Selective Anti-proliferation Effects Against Hepatoma Cells

Objective To study whether isoniazid combined with doxorubicin can effect on the proliferation of the hepatoma cells and normal liver cells and providing scientific proof of such combination protocols.Methods HepG2 and L-02 were cultured in different doses,and the cell proliferation ability was determined by Sulfonyl rhodamine B(SRB)method,the optimal dose was obtained.The control group without drug intervention,isoniazid group,doxorubicin group,isoniazid + doxorubicin combined group were divided into and treated accordingly.The intracellular reactive oxygen concentration,rGSH level,rGSH/GSSG ratio and the result of Western blotting were detected to explore the mechanism selective inhibition of proliferation of HepG2 cells.Results Compared with the L-02,the combination of isoniazid and doxorubicin inhibited the proliferation of HepG2 cells significantly(P<0.05),induced more reactive oxygen species(P<0.05),the intracellular rGSH and rGSH/GSSG ratio were reduced(P<0.05);compared with other HepG2 groups,the intracellular Nrf2 protein expression of the combined group decreased,but the nuclear Nrf2 protein expression increased.Conclusion Isoniazid combined with doxorubicin inhibits reactive oxygen species clearance and reduces reducing glutathione.It can selectively inhibit the proliferation of HepG2 cells;although the high oxidative stress state can selectively activate the Nrf2/ARE pathway,it can not alleviate the inhibition of hepatoma cell proliferation by high ROS level.