2. Academic Validation
  3. C-X-C motif chemokine receptor 4 inhibition promotes the effect of plantamajoside in hepatocellular carcinoma

C-X-C motif chemokine receptor 4 inhibition promotes the effect of plantamajoside in hepatocellular carcinoma

  • Arab J Gastroenterol. 2024 Jan 13:S1687-1979(23)00111-9. doi: 10.1016/j.ajg.2023.12.001.
Jiajia Sun 1,  Wei Liu 2,  Hao Fu 3,  Yibei Li 4,  Jiaqi Huang 4,  Yuxi Wang 4,  Lei Zhu 5
Affiliations

Affiliations

  • 1 General Surgery Department of Characteristic Medical Center of PAP, Tianjin 300162, China.
  • 2 Emergency Medicine Department of Shandong Corps Hospital of PAP, Shandong 250000, China.
  • 3 Reproductive Department of Characteristic Medical Center of PAP, Tianjin 300162, China.
  • 4 Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
  • 5 Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: rm003258@whu.edu.cn.
PMID: 38220479 DOI: 10.1016/j.ajg.2023.12.001
Abstract

Background and study aim: Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide, and, more than half of these cases are diagnosed in China. However, effective treatment for HCC is still limited.

Material and methods: C-X-C motif Chemokine Receptor 4 (CXCR4) was first activated and inhibited in HepG2 cells using a pharmacological method. HepG2 cell proliferation was detected using the CCK-8 method. Metastasis and Apoptosis of HepG2 cells were detected using wound healing and flow cytometry. The expression of each target molecule related to metastasis and invasion, such as MMPs, E-cadherin and the PI3K/Akt/Mcl-1/PARP signaling pathway was detected by western blotting. The secretion of molecular metastases was detected using competitive ELISA.

Results: This study constructed a CXCR4 activation and inhibition model in HepG2 cells. CXCR4 inhibition promoted the inhibitory effect of plantamajoside on the proliferation and metastasis of cells, which led to Apoptosis. Furthermore, we found that the expression of apoptosis-related proteins was increased after treatment with plantamajoside combined with CXCR4 inhibition. In addition, the expression and secretion of pro-metastatic proteins, including MMPs and E-cadherin were decreased. We also noticed that this effect might be mediated by the PI3K/Akt/Mcl-1/PARP signaling pathway.

Conclusion: CXCR4 inhibition may contribute to the treatment of HCC. Inhibition of CXCR4 expression contributes to the therapeutic effect of plantamajoside; the effect of plantamajoside might be mediated by the PI3K/Akt/Mcl-1/PARP signaling pathway; and CXCR4 might be a therapeutic target of HCC.

Keywords

Apoptosis; CXCR4; Hepatocellular carcinoma; Inflammation; Plantamajoside.

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