DUSP10通过增强肝癌细胞干性促进对仑伐替尼耐药的实验研究*

doi:10.3969/j.issn.1672-5069.2025.04.004

Abstract

Abstract: Objective This experiment aimed to investigate the mechanism by which dual specificity protein phosphatases 10(DUSP10) mediates lenvatinib resistance by through regulating stemness characteristics in hepatocellular carcinoma (HCC) in vitro. Methods Lenvatinib-resistant cell lines, e.g., Huh7-resistant and Hep3B-resistant, were established, and stable DUSP10-overexpressing (Huh7 and PLC/PRF/5) and knockdown (Huh7-resistant, Hep3B-resistant, Hep-12) cell models were constructed. Western blot was conducted to detect stemness markers (Nanog, BMI1, ABCG2) expression, and CCK-8 assay was performed to determine IC50 values and calculate the resistance index (RI). Results DUSP10 expression in resistant cell lines was up-regulated by 2.1 to 3.8 fold compared to in wild-type cells (P<0.01); overexpression of DUSP10 increased the IC50 of lenvatinib in Huh7 cells from 1.376 μM to 28.44 μM (RI=20.67) and in PLC/PRF/5 cells from 4.118 μM to 18.01 μM (RI=4.37), accompanied by a 1.5 to 2.3 fold up-regulation of stemness genes; conversely, DUSP10 knockdown reduced the IC50 in Huh7-resistant, Hep3B-resistant, and Hep-12 cells by 6.53 fold, 12.02 fold, and 3.29 fold, respectively (all P<0.001), with a 40% to 60% down-regulation of stemness genes. Conclusion DUSP10 significantly decreases the sensitivity of HCC cells to lenvatinib by probably up-regulating stemness-related genes, such as Nanog/BMI1/ABCG2, and targeting the DUSP10-stemness pathway might reverse drug resistance.

Key words: Hepatocellular carcinoma, Cancer stem cells, Dual specificity protein phosphatases 10, Stemness, Lenvatinib, Drug resistance, In vitro

Li Ang, Yang Xiaodan. Mechanistic of DUSP10-mediated lenvatinib resistance in hepatocellular carcinoma by through cancerous stem cell regulation[J]. Journal of Practical Hepatology, 2025, 28(4): 493-496.

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Mechanistic of DUSP10-mediated lenvatinib resistance in hepatocellular carcinoma by through cancerous stem cell regulation

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