Background/Objectives: Sorafenib and lenvatinib are tyrosine kinase inhibitors used in hepatocellular carcinoma (HCC) treatment. This study investigates how hepatitis B virus (HBV) infection affects their efficacy in HepG2 hepatoma cells.Methods: HepG2 and HBV-infected HepG2/2215 cells were treated with varying concentrations of both drugs. The cell viability, cell cycle gene expression, cycle progression, and phosphorylation levels of ERK and AKT were analyzed. Results: The HBV-infected cells showed significant alterations in their cell cycle gene expressions, with an 80-fold increase in CCND2 expression and a higher proportion of cells in the G2/M phase, indicating enhanced proliferation. While both drugs decreased HepG2 cell viability in a concentration-dependent manner, HBV infection conferred resistance, as evidenced by the increased viable cells in the HepG2/2215 cultures. Sorafenib and lenvatinib decreased key cyclin and cyclin-dependent kinase expressions in uninfected cells, with less effect on the HBV-infected cells. Both drugs lowered the pERK and pAKT levels in the HepG2 cells. In the HBV-infected cells, sorafenib reduced the pERK and pAKT levels to a lesser extent. However, treatment with lenvatinib elevated the levels of pERK and pAKT.Conclusions: In conclusion, HBV infection increases resistance to both sorafenib and lenvatinib in hepatoma cells by influencing the cell cycle regulatory genes and critical signaling pathways. However, the resistance mechanisms likely differ between the two medications.
背景/目的：索拉非尼和仑伐替尼是用于肝细胞癌治疗的酪氨酸激酶抑制剂。本研究探讨乙型肝炎病毒感染如何影响其在HepG2肝癌细胞中的疗效。方法：用不同浓度的两种药物处理HepG2细胞和HBV感染的HepG2/2215细胞。分析细胞活力、细胞周期基因表达、周期进程以及ERK和AKT的磷酸化水平。结果：HBV感染的细胞在细胞周期基因表达上表现出显著改变，CCND2表达增加80倍，G2/M期细胞比例更高，表明增殖增强。虽然两种药物均以浓度依赖的方式降低HepG2细胞活力，但HBV感染赋予了耐药性，这体现在HepG2/2215培养物中活细胞数量增加。索拉非尼和仑伐替尼降低了未感染细胞中关键细胞周期蛋白和细胞周期蛋白依赖性激酶的表达，但对HBV感染细胞的影响较小。两种药物均降低了HepG2细胞中的pERK和pAKT水平。在HBV感染的细胞中，索拉非尼对pERK和pAKT水平的降低程度较小。然而，仑伐替尼处理却提高了pERK和pAKT的水平。结论：总之，HBV感染通过影响细胞周期调控基因和关键信号通路，增加了肝癌细胞对索拉非尼和仑伐替尼的耐药性。然而，两种药物的耐药机制可能有所不同。
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