Hydrazinocurcumin and 5-fluorouracil enhance apoptosis and restrain tumorigenicity of HepG2 cells via disrupting the PTEN-mediated PI3K/Akt signaling pathway.

In this study, we investigate the role and mechanism of HZC in regulating HepG2 cell apoptosis and tumorigenicity, and its synergistic effects with 5-fluorouracil (5-Fu). HepG2 cells were treated with HZC and/or 5-Fu to analyze the possible synergistic effects on cell proliferation, apoptosis and cell cycle distribution in vitro using EdU staining, Hoechst staining and flow cytometry, respectively. For mechanistic investigation we used pic, a phosphatase and tensin homolog (PTEN) inhibitor, and in other studies assessed the expression pattern of PTEN and PI3K/Akt signaling pathway-related genes. Additionally, we tested in vivo effects of HZC and 5-Fu treatment on growth of HepG2 cell tumors in nude mice. We found that HZC or 5-Fu induced apoptosis and repressed proliferation of HepG2 cells by upregulating the expression of PTEN and disrupting the PI3K/Akt signaling pathway activation. Moreover, HZC had a higher pro-apoptotic effect than 5-Fu. HZC and 5-Fu induced HepG2 cell apoptosis and inhibited their tumorigenicity in vivo. Inhibition of PTEN expression activated the PI3K/Akt signaling pathway and reversed the protective effects of HZC or 5-Fu. Thus, HZC and 5-Fu increase PTEN, which blocks the PI3K/Akt signaling pathway, ultimately inducing HepG2 cell apoptosis. Importantly, the synergistic combination of HZC and 5-Fu may present promising strategy for the treatment of HCC. PMID: 32559627 [PubMed - as supplied by publisher]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research