Sorafenib-irinotecan sequential therapy augmented the anti-tumor efficacy of monotherapy in hepatocellular carcinoma cells HepG2

Neoplasma
Z WangYi-Xin Zhang

Abstract

The current study aimed to evaluate the efficacy of sorafenib-based combined therapy against hepatocellular carcinoma (HCC). HepG2 cells were exposed to sorafenib, irinotecan, and oxaliplatin and then subjected to MTT assay to determine chemosensitivity. Flow cytometry was used to examine cell cycle distribution and cell apoptosis. Levels of cleaved caspase-8, -3, and PARP were determined by Western blot. Real-time PCR and Western blot were used to determine p53 expression, respectively. The efficacy of combined therapy were verified in nude mice bearing HepG2 xenografts. HepG2 cells used in the current study were sensitive to sorafenib, irinotecan, and oxaliplatin. Sorafenib arrested cell cycle in S phase and the peak effect appeared at 30 h post treatment. Sorafenib exposure for 30 h followed by irinotecan exposure for 48 h synergistically induced cell apoptosis in HepG2 cells. On the other hand, sorafenib-oxaliplatin sequential exposure for the same time only acted an additive effect in soliciting cell apoptosis. Sorafenib and irinotecan sequential treatment significantly increased the levels of cleaved caspase-8, -3, and PARP in HepG2 cells. Sorafenib suppressed p53 expression at both mRNA and protein levels, which might co...Continue Reading

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