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

  • Cancers (Basel). 2023 Oct 22;15(20):5097. doi: 10.3390/cancers15205097.
Zu-Yau Lin  1  2  3  4 ,  Ming-Lun Yeh  1  2  3  4 ,  Po-Cheng Liang  1 ,  Po-Yao Hsu  1 ,  Chung-Feng Huang  1  2  3  4 ,  Jee-Fu Huang  1  2  3  4 ,  Chia-Yen Dai  1  2  3  4 ,  Ming-Lung Yu  1  2  5  6 ,  Wan-Long Chuang  1  2  3  4
Affiliations
  • 1. Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
  • 2. Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 3. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 4. Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 5. School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan.
  • 6. School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine, Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung 804201, Taiwan.
PMID: 37894463 DOI: 10.3390/cancers15205097
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
NANOG; colchicine; dose-dependent effect; hepatocellular carcinoma; lenvatinib; multikinase inhibitor.
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