The inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and corresponding mechanism / 中国药理学通报

ABSTRACT

Aim To explore the inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and the mechanism.Methods Mouse model of subcutaneous liver cancer was used.Single agent of lenvatinib, single agent of fluvastatin, a combination of lenvatinib and fluvastatin and control solvent were given to four groups of mice.Tumor volume was measured.Immunohistochemistry was used to examine proliferation of tumor cells.Tunel was employed to detect the cell apoptosis.qRT-PCR and immunohistochemistry were used to measure the expression of TLR4.Western blot was employed to determine β-catenin expression.Rescue experiment was done using human hepatoma cells cultured in vitro.Results Treatment with both lenvatinib and fluvastatin significantly suppressed tumor growth in nude mice.Combined treatment significantly decreased the expressions of PNCA and increased apoptosis in tumor cells.Mechanically combined treatment synergistically suppressed the mRNA and protein expression of TLR4 which further inhibited the expression of β-catenin in hepatoma cells.Conclusions A combination of lenvatinib and fluvastatin synergistically inhibits tumor growth and promotes tumor cell apoptosis.The combination treatment significantly inhibits TLR4/β-catenin signaling pathway.