Role of the HIF-1α/BNIP3 Signaling Pathway in Recurrent Hepatocellular Carcinoma and the Mechanism of Traditional Chinese Medicine

J Hepatocell Carcinoma. 2023 Jun 8:10:893-908. doi: 10.2147/JHC.S409292. eCollection 2023.

Abstract

Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.

Keywords: HIF-1α/BNIP3 signaling pathway; autophagy; hypoxia; recurrent hepatocellular carcinoma; traditional Chinese medicine.

Publication types

  • Review

Grants and funding

This work was supported by the QI Huang Scholars (National Chinese Medicine Human Education Letter 2022-6); the Major Public Welfare Special Project of Henan Province (201300310100); and the Joint Open Project of the State Administration of Traditional Chinese Medicine (GZY-KJS-2022-040-1).