Hydrazinocurcumin and 5-fluorouracil enhance apoptosis and restrain tumorigenicity of HepG2 cells via disrupting the PTEN-mediated PI3K/Akt signaling pathway - 28/08/20
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Graphical abstract |
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.
Highlights |
• | Hydrazinocurcumin and 5-Fu induce HepG2 cell apoptosis but inhibit its proliferation. |
• | Hydrazinocurcumin and 5-Fu upregulate PTEN to inhibit the PI3K/Akt signaling pathway. |
• | Hydrazinocurcumin and 5-Fu prevent the tumorigenicity of HepG2 cells. |
• | Hydrazinocurcumin and 5-Fu protect liver function of tumor-bearing mice. |
• | Hydrazinocurcumin exhibits promise as a therapeutic agent for HCC. |
Abstract |
Hydrazinocurcumin (HZC), a curcumin analogue, serves as a tumor suppressor in breast cancer and lung cancer. 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.
El texto completo de este artículo está disponible en PDF.Keywords : Hydrazinocurcumin, Hepatocellular carcinoma, 5-fluorouracil, Phosphatase and tensin homolog, PI3K/Akt signaling pathway, Cell apoptosis
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Vol 129
Artículo 109851- septembre 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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