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

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.

Keywords

• colchicine
• dose-dependent effect
• hepatocellular carcinoma
• lenvatinib
• multikinase inhibitor
• <i>NANOG</i>