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阿帕替尼通过抑制表皮生长因子受体/应激活化蛋白激酶/细胞外信号调节激酶信号通路来调节对索拉非尼耐药的肝细胞癌。

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

作者信息

Fan Dexue, Su Wei, Bi Zhaowen, Wang Xinxing, Xu Xianwen, Ma Mingze, Zhu Lichao, Zhang Zhenhai, Gao Junlin

机构信息

Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.

Liver Gall Bladder and Pancreatic Surgery Ward, Qinghai Red Cross Hospital, Xining, 810001, China.

出版信息

Oncol Res. 2025 May 29;33(6):1459-1472. doi: 10.32604/or.2025.060407. eCollection 2025.

DOI:10.32604/or.2025.060407
PMID:40486881
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12144613/
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 and . 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 and . 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.

摘要

目的：据报道，阿帕替尼对索拉非尼耐药的肝细胞癌（HCC）患者是一种有前景的治疗方法。然而，其潜在机制仍不明确。本研究旨在探讨阿帕替尼对索拉非尼耐药HCC的疗效及其潜在机制。 方法：观察HepG2和HepG2/索拉非尼细胞的上皮-间质转化（EMT）变化后，我们用不同浓度的阿帕替尼处理它们，以评估其对索拉非尼耐药HCC的影响。随后，引入c-Jun氨基末端激酶（JNK，SP600125）和细胞外信号调节激酶（ERK，PD98059）的特异性抑制剂，以研究阿帕替尼是否通过调节表皮生长因子受体（EGFR）/JNK/ERK信号通路影响索拉非尼耐药HCC。通过细胞计数试剂盒-8（CCK-8）、集落形成、Transwell和免疫荧光试验评估生物学行为变化。同时，进行蛋白质印迹分析以阐明与EMT和EGFR/JNK/ERK信号通路相关的蛋白质表达。 结果：与HepG2细胞相比，HepG2/索拉非尼细胞对索拉非尼表现出更大的耐药性，且索拉非尼耐药HCC的特征是EMT变化。阿帕替尼对HepG2/索拉非尼细胞的生物学行为表现出浓度依赖性抑制，对HepG2细胞影响最小。此外，阿帕替尼对索拉非尼耐药细胞中EMT相关蛋白表达的影响与索拉非尼敏感细胞相似。此外，在阿帕替尼处理组中，与EGFR/JNK/ERK通路相关的蛋白质表达呈剂量依赖性降低。值得注意的是，SP600125和PD98059有助于阿帕替尼在索拉非尼耐药HCC中抑制EMT和EGFR/JNK/ERK通路相关蛋白。 结论：阿帕替尼可能通过抑制EMT和EGFR/JNK/ERK通路来阻碍索拉非尼耐药HCC的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/3b989443b04b/OncolRes-33-60407-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/f7e9a1fdffed/OncolRes-33-60407-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/11f875ec1f62/OncolRes-33-60407-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/e97623be8b50/OncolRes-33-60407-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/d14fa8f2e8cc/OncolRes-33-60407-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/5ad862ba84d2/OncolRes-33-60407-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/af8812814eab/OncolRes-33-60407-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/411b1b44c536/OncolRes-33-60407-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/3b989443b04b/OncolRes-33-60407-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/f7e9a1fdffed/OncolRes-33-60407-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/11f875ec1f62/OncolRes-33-60407-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/e97623be8b50/OncolRes-33-60407-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/d14fa8f2e8cc/OncolRes-33-60407-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/5ad862ba84d2/OncolRes-33-60407-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/af8812814eab/OncolRes-33-60407-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/411b1b44c536/OncolRes-33-60407-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/12144613/3b989443b04b/OncolRes-33-60407-f008.jpg

相似文献

[1]
Apatinib modulates sorafenib-resistant hepatocellular carcinoma through inhibiting the EGFR/JNK/ERK signaling pathway.

Oncol Res. 2025-5-29

[2]
CRIPTO promotes an aggressive tumour phenotype and resistance to treatment in hepatocellular carcinoma.

J Pathol. 2018-5-9

[3]
Regorafenib reverses HGF-induced sorafenib resistance by inhibiting epithelial-mesenchymal transition in hepatocellular carcinoma.

FEBS Open Bio. 2019-1-18

[4]
EGFR signaling confers resistance to BET inhibition in hepatocellular carcinoma through stabilizing oncogenic MYC.

J Exp Clin Cancer Res. 2019-2-15

[5]
Activation of phosphatidylinositol 3-kinase/AKT/snail signaling pathway contributes to epithelial-mesenchymal transition-induced multi-drug resistance to sorafenib in hepatocellular carcinoma cells.

PLoS One. 2017-9-21

[6]
The monoclonal antibody CH12 enhances the sorafenib-mediated growth inhibition of hepatocellular carcinoma xenografts expressing epidermal growth factor receptor variant III.

Neoplasia. 2012-6

[7]
Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation.

BMC Cancer. 2015-11-30

[8]
Anti‑cancer effects of a novel Pan‑RAF inhibitor in a hepatocellular carcinoma cell line.

Mol Med Rep. 2018-2-16

[9]
Coupling HDAC4 with transcriptional factor MEF2D abrogates SPRY4-mediated suppression of ERK activation and elicits hepatocellular carcinoma drug resistance.

Cancer Lett. 2021-11-1

[10]
KIAA1199 promotes sorafenib tolerance and the metastasis of hepatocellular carcinoma by activating the EGF/EGFR-dependent epithelial-mesenchymal transition program.

Cancer Lett. 2019-4-11

本文引用的文献

[1]
Prognostic Significance of the Royal Marsden Hospital (RMH) Score in Patients with Cancer: A Systematic Review and Meta-Analysis.

Cancers (Basel). 2024-5-11

[2]
MYC in liver cancer: mechanisms and targeted therapy opportunities.

Oncogene. 2023-11

[3]
Artesunate Sensitizes human hepatocellular carcinoma to sorafenib via exacerbating AFAP1L2-SRC-FUNDC1 axis-dependent mitophagy.

Autophagy. 2024-3

[4]
Advances in the Early Detection of Hepatobiliary Cancers.

Cancers (Basel). 2023-7-30

[5]
Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study.

Lancet. 2023-9-30

[6]
KIAA1429 mediates epithelial mesenchymal transition in sorafenib-resistant hepatocellular carcinoma through m6A methylation modification.

Cancer Med. 2023-3

[7]
Tumor-associated macrophages promote resistance of hepatocellular carcinoma cells against sorafenib by activating CXCR2 signaling.

J Biomed Sci. 2022-11-21

[8]
Ribosomal protein L22-like1 (RPL22L1) mediates sorafenib sensitivity via ERK in hepatocellular carcinoma.

Cell Death Discov. 2022-8-17

[9]
The deadly cross-talk between Hippo pathway and epithelial-mesenchymal transition (EMT) in cancer.

Mol Biol Rep. 2022-10

[10]
Increased mitochondrial fission drives the reprogramming of fatty acid metabolism in hepatocellular carcinoma cells through suppression of Sirtuin 1.

Cancer Commun (Lond). 2022-1

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