2. Academic Validation
  3. Low Pi stress enhances the sensitivity of hepatocellular carcinoma to sorafenib

Low Pi stress enhances the sensitivity of hepatocellular carcinoma to sorafenib

  • Biochem Pharmacol. 2023 May 15;115593. doi: 10.1016/j.bcp.2023.115593.
Qiu-Chen Bi 1,  Zhi-Qiang Deng 2,  Yang-Feng Lv 1,  Yue Liu 3,  Chuan-Sheng Xie 3,  Yuan-Qiao He 4,  Qun Tang 5
Affiliations

Affiliations

  • 1 Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China; Institute for Advanced Study, Nanchang University, Nanchang, China.
  • 2 Department of Oncology, the First People's Hospital of Fuzhou, Fuzhou, China.
  • 3 Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China.
  • 4 Department of Laboratory Animal Science, Nanchang University, Nanchang, China.
  • 5 Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China; Institute for Advanced Study, Nanchang University, Nanchang, China. Electronic address: tangqun@ncu.edu.cn.
PMID: 37196682 DOI: 10.1016/j.bcp.2023.115593
Abstract

Sorafenib is a tyrosine kinase inhibitor for the treatment of advanced-stage HCC; however, clinical trials of sorafenib failed to demonstrate long-term survival benefits due to drug resistance. Low Pi stress has been shown to inhibit tumor growth and the expression of multidrug resistance-associated proteins. In this study, we investigated the sensitivity of HCC to sorafenib under conditions of low Pi stress. As a result, we found that low Pi stress facilitated sorafenib-mediated suppression of migration and invasion of HepG-2 and Hepa1-6 cells by decreasing the phosphorylation or expression of Akt, ERK and MMP-9. Angiogenesis was inhibited due to decreased expression of PDGFR under low Pi stress. Low Pi stress also decreased the viability of sorafenib-resistant cells by directly regulating the expression of Akt, HIF-1a and p62. In vivo drug sensitivity analysis in the four animal models showed a similar tendency that low Pi stress enhances sorafenib sensitivity in both the normal and drug-resistant models. Altogether, low Pi stress enhances the sensitivity of hepatocellular carcinoma to sorafenib and expands the indications for sevelamer.

Keywords

Inorganic phosphate; drug-resistant; hepatocellular carcinoma; sorafenib.

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