Lobaplatin promotes 125I-induced apoptosis and inhibition of proliferation in hepatocellular carcinoma by upregulating PERK-eIF2α-ATF4-CHOP pathway

We investigated the mechanism underlying the effect of a combination treatment of 125 I radioactive seed implantation and lobaplatin (LBP) in hepatocellular carcinoma. The effects of administration of HCC cells and subcutaneous tumor model of mice with different doses of 125 I or a sensitizing concentration of LBP alone, or in combination, on cellular apoptosis and proliferation were analyzed and it was confirmed that LBP promotes 125 I-induced apoptosis and inhibition of proliferation of HCC. Furthermore, isobaric tag for relative and absolute quantification labeling analyses suggested that 125 I promoted the apoptosis and inhibition of proliferation of HCC cells by upregulating the expression of PERK-eIF2α-ATF4-CHOP pathway, a well-known apoptosis-related pathway. Moreover, LBP was found to boost the 125 I-induced upregulation of this pathway and increase the apoptosis. Our data indicate that LBP promotes the apoptotic and anti-proliferative effects of 125 I and provide a firm foundation for better clinical application of this combination therapy.