Dose Consideration of Lenvatinib’s Anti-Cancer Effect on Hepatocellular Carcinoma and the Potential Benefit of Combined Colchicine Therapy

SIMPLE SUMMARY: The long-term benefits of lenvatinib on the treatment of advanced hepatocellular carcinoma (HCC) are still unsatisfactory. The search for a new drug to promote lenvatinib’s anti-cancer effect is an urgent issue. Whether the response of HCC to lenvatinib is dose-dependent also still needs to be clarified. The aims of this study were to investigate the dose-dependent anti-cancer effect of lenvatinib on HCC cells and the potential benefit of combined colchicine therapy. Four primary cultured HCC cell lines were applied for experiments. Combined analysis of the results of differential expressions of the genes (11 lenvatinib target genes and NANOG) and the anti-proliferative effect indicated that the anti-cancer effect of lenvatinib on HCC was not dose dependent. Combined clinically achievable plasma colchicine concentration with lenvatinib can promote the total anti-cancer effects on HCC. ABSTRACT: Purpose: The dose-dependent anti-cancer effect of lenvatinib on hepatocellular carcinoma (HCC) cells and the potential benefit of combined colchicine therapy were investigated. Methods: Four primary cultured HCC (S103, S143, S160, S176) cell lines were investigated by differential expressions of genes (11 lenvatinib target genes and NANOG) and anti-proliferative effect using clinically achievable plasma lenvatinib (250, 350 ng/mL) and colchicine (4 ng/mL) concentrations. Results: Colchicine showed an anti-proliferative effect on all cell lines. Lenvatinib at 250 ng/mL inhibited proliferation in all cell lines, but 350 ng/mL inhibited only three cell lines. For lenvatinib target genes, colchicine down-regulated more genes and up-regulated less genes than lenvatinib did in three cell lines. Lenvatinib up-regulated NANOG in all cell lines. Colchicine down-regulated NANOG in three cell lines but up-regulated NANOG with less magnitude than lenvatinib did in S103. Overall, combined colchicine and 250 ng/mL lenvatinib had the best anti-cancer effects in S143, with similar effects with combined colchicine and 350 ng/mL lenvatinib in S176 but less effects than combined colchicine and 350 ng/mL lenvatinib in S103 and S160. Conclusions: Lenvatinib does not show a dose-dependent anti-cancer effect on HCC. Combined colchicine and lenvatinib can promote the total anti-cancer effects on HCC.