Submit

Login Login

Register Register

Home / Journals / OR / Online First / doi:10.32604/or.2025.060407
Journal Menu
Special Issues
Table of Content

All issues

Online First

2025

2024

2023

2022

2021

2020

2019

2018

2017

2016

2015

Past Issues

Open Access

ARTICLE

Apatinib modulates sorafenib-resistant hepatocellular carcinoma through inhibiting the EGFR/JNK/ERK signaling pathway

DEXUE FAN1,#, WEI SU2,#, ZHAOWEN BI3, XINXING WANG1, XIANWEN XU1, MINGZE MA4, LICHAO ZHU5, ZHENHAI ZHANG1,3,*, JUNLIN GAO2,*
1 Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China
2 Liver Gall Bladder and Pancreatic Surgery Ward, Qinghai Red Cross Hospital, Xining, 810001, China
3 Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China
4 Departments of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China
5 Department of Pediatric Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China
* Corresponding Author: ZHENHAI ZHANG. Email: email; JUNLIN GAO. Email: email
# These two authors contributed equally to this work
(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research https://doi.org/10.32604/or.2025.060407

Received 31 October 2024; Accepted 03 January 2025; Published online 05 March 2025

Abstract

Objectives: Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma (HCC) patients. However, the underlying mechanism remains ambiguous. The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both in vitro and in vivo. Methods: After observing epithelial-mesenchymal transformation (EMT) changes in HepG2 and HepG2/Sorafenib cells, we treated them with varying concentrations of apatinib to assess its impact on sorafenib-resistant HCC. Subsequently, specific inhibitors of c-Jun N-terminal kinase (JNK, SP600125) and extracellular signal-regulated kinase (ERK, PD98059) were introduced to investigate whether apatinib influenced sorafenib-resistant HCC via modulation of the epidermal growth factor receptor (EGFR)/JNK/ERK signaling pathway in vitro and in vivo. Biological behavior changes were assessed through cell counting kit-8 (CCK-8), colony formation, transwell, and immunofluorescence tests. Simultaneously, Western blot analysis was conducted to elucidate the expression of proteins associated with EMT and the EGFR/JNK/ERK signaling pathway. Results: The HepG2/Sorafenib cells exhibited greater resistance to sorafenib compared to HepG2 cells, and sorafenib-resistant HCC was characterized by EMT changes. Apatinib demonstrated concentration-dependent inhibition of biological behaviors in HepG2/Sorafenib cells, with minimal impact on HepG2 cells. Additionally, apatinib had a pronounced effect on the expression of EMT-related proteins in sorafenib-resistant cells similar to that in sorafenib-sensitive cells. Furthermore, there was a dose-dependent reduction in the expression of proteins associated with the EGFR/JNK/ERK pathway in apatinib-treated groups. Notably, SP600125 and PD98059 contributed to the inhibition of EMT and EGFR/JNK/ERK pathway-related proteins by apatinib in sorafenib-resistant HCC. Conclusion: Apatinib potentially hindered the progression of sorafenib-resistant HCC by suppressing both EMT and the EGFR/JNK/ERK pathway.

Keywords

Apatinib; Sorafenib resistance; EGFR/JNK/ERK; Epithelial mesenchymal transformation; Hepatocellular carcinoma (HCC)

  • 226

    View

  • 58

    Download

  • 0

    Like

Related articles

Share Link