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Apatinib reduces liver cancer cell multidrug resistance by modulating nf-κb signaling pathway

bIOCELL 2024年第9期48卷 1331-1341页

作者： He, Xiaoxiao Zhou, Xueqing Zhang, Jinpeng Zhang, Mingfei Zeng, Danhong Zhang, Heng Yang, Shucai Huazhong Univ Sci & Technol Cent Hosp Wuhan Tongji Med Coll Dept Gastroenterol Wuhan 430022 Peoples R China Southern Med Univ Pingshan Hosp Pingshan Dist Peoples Hosp Shenzhen Dept Clin Lab Shenzhen 518118 Peoples R China

Objectives: This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro. Methods: To establish a Hep3b/5-Fu resistant cell line, 5-Fu concentrations were gradually increased in the culture media. Hep3b/5-Fu cells drug resistance and its alleviation by apatinib were confirmed via flow cytometry and Cell Counting Kit 8 (CCK8) test. Further, Nuclear factor kappa b (nf-kappa b) siRNA was transfected into Hep3b/5-Fu cells to assess alterations in the expression of multidrug resistance (MDR)-related genes and proteins. Nude mice were injected with Hep3b/5-Fu cells to establish subcutaneous xenograft tumors and then categorized into 8 treatment groups. The treatments included oxaliplatin, 5-Fu, and apatinib. In the tumor tissues, the expression of MDRrelated genes was elucidated via qRT-PCR, immunohistochemistry, and Western blot analyses. Results: The apatinibtreated mice indicated slower tumor growth with smaller size compared to the control group. both the in vivo and in vitro investigations revealed that the apatinib-treated groups had reduced expression of MDR genes GST-pi, LRP, MDR1, and p-p65. Conclusions: Apatinib effectively suppresses MDR in human hepatic cancer cells by modulating the expression of genes related to MDR, potentially by suppressing the nf-kappa b signaling pathway.

关键词： Apatinib Liver cancer Multidrug resistance nf-kappa b signaling pathway DRUG-RESISTANCE CHEMOTHERAPY SENSITIVITY EXPRESSION ADENOCARCINOMA PROGRESS THERAPY GENE

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