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Home / Journals / BIOCELL / Online First / doi:10.32604/biocell.2024.052625
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ARTICLE

Apatinib reduces liver cancer cell multidrug resistance by modulating NF-κB signaling pathway

XIAOXIAO HE1, XUEQING ZHOU2, JINPENG ZHANG2, MINGFEI ZHANG2, DANHONG ZENG2, HENG ZHANG1, SHUCAI YANG2,*
1 Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
2 Department of Clinical Laboratory, Pingshan Hospital, Southern Medical University (Pingshan District People’s Hospital of Shenzhen), Shenzhen, 518118, China
* Corresponding Author: SHUCAI YANG. Email: email

BIOCELL https://doi.org/10.32604/biocell.2024.052625

Received 09 April 2024; Accepted 05 June 2024; Published online 03 July 2024

Abstract

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-κB) 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 MDR-related genes was elucidated via qRT-PCR, immunohistochemistry, and Western blot analyses. Results: The apatinib-treated 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-κB signaling pathway.

Keywords

Apatinib; Liver cancer; Multidrug resistance; NF-κB signaling pathway

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