文章：

乐伐替尼对肝细胞癌的抗癌效应剂量考量及联合秋水仙碱治疗的潜在益处

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

原文发布日期：22 October 2023

DOI: 10.3390/cancers15205097

类型: Article

开放获取: 是

英文摘要：

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 andNANOG) 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-regulatedNANOGin all cell lines. Colchicine down-regulatedNANOGin three cell lines but up-regulatedNANOGwith 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.

摘要翻译： 

目的：本研究旨在探讨乐伐替尼对肝细胞癌（HCC）细胞的剂量依赖性抗癌作用，以及联合秋水仙碱治疗的潜在获益。方法：通过检测四种原代培养的HCC细胞系（S103、S143、S160、S176）中基因（11个乐伐替尼靶基因及NANOG）的差异表达，并利用临床可达到的血浆药物浓度（乐伐替尼250、350 ng/mL；秋水仙碱4 ng/mL）评估其抗增殖效应。结果：秋水仙碱对所有细胞系均显示出抗增殖作用。250 ng/mL的乐伐替尼抑制了所有细胞系的增殖，而350 ng/mL仅抑制了三种细胞系。在乐伐替尼靶基因表达方面，在三种细胞系中秋水仙碱相比乐伐替尼下调了更多基因、上调了更少基因。乐伐替尼在所有细胞系中均上调NANOG表达。秋水仙碱在三种细胞系中下调NANOG表达，而在S103细胞系中虽上调NANOG，但上调幅度低于乐伐替尼。总体而言，秋水仙碱联合250 ng/mL乐伐替尼在S143细胞系中抗癌效果最佳；在S176细胞系中，该联合方案与秋水仙碱联合350 ng/mL乐伐替尼效果相当；而在S103和S160细胞系中，其效果弱于秋水仙碱联合350 ng/mL乐伐替尼。结论：乐伐替尼对HCC未呈现剂量依赖性抗癌效应。秋水仙碱联合乐伐替尼治疗可增强对HCC的整体抗癌效果。

原文链接：

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