OBJECTIVE Hepatocel ular carcinoma(HCC)is the most common cause of cancer-related mortality,with high incidence rates,robust metastatic propensity and acquired resistance to therapy.Metformin,an extensively prescribed...OBJECTIVE Hepatocel ular carcinoma(HCC)is the most common cause of cancer-related mortality,with high incidence rates,robust metastatic propensity and acquired resistance to therapy.Metformin,an extensively prescribed and well-tolerated first-linetherapeutic drug for type 2 diabetes mellitus,has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutics to improve treatment efficacy and lower doses.Curcumin,a botanical extracts,has been shown antitumorigenic properties.This study aims to investigate the combinational effect of metformin and curcumin on inbibition of tumor growth and metastasis in Hep G2 cells and the possible underlying mechanisms.METHODS The cell proliferation was determined by MTT,CCK-8 and colony formation assay.The protein expression was detected by Western blotting.Activity of MMP-2 and MMP-9 was estimated by gelatin zymography.Flow cytometry analysis was used to evaluate the influence of metformin and curcumin on cell cycle arrest and apoptosis,and morphology observation of apoptosis was detected by Hoechst33342.Scratch and transwell assay was performed to detect the cell migration and invasion.The suppression of this combination therapy oncapillary tube formation was detected by tube formation assay.RESULTS Combination of metformin and curcumin induced stronger inhibition on Hep G2 cells proliferation than monotherapywhich related to induction of cell cycle arrest in G2/M phase and apoptosis through regulation of the protein expression of cyclin B and Bcl-2/Bax.Moreover,the co-treatment of metformin with curcumin exerted an enhanced inhibitory effect on Hep G2 cell metastasis and synergistically inhibited the tube formation of HUVEC cells.The suppression of PI3K/AKT/m TOR pathway and inhibition the protein expression of STAT3,MMP9,MMP2 and VEGF might involve in this synergistic effects of combination treatment.CONCLUSION Combination of metformin and curcumin inhibited Hep G2 cells proliferationmore effectively than monotherapy and synergistically induced a greater inhibition on migration and invasion of Hep G2 cells.展开更多
文摘OBJECTIVE Hepatocel ular carcinoma(HCC)is the most common cause of cancer-related mortality,with high incidence rates,robust metastatic propensity and acquired resistance to therapy.Metformin,an extensively prescribed and well-tolerated first-linetherapeutic drug for type 2 diabetes mellitus,has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutics to improve treatment efficacy and lower doses.Curcumin,a botanical extracts,has been shown antitumorigenic properties.This study aims to investigate the combinational effect of metformin and curcumin on inbibition of tumor growth and metastasis in Hep G2 cells and the possible underlying mechanisms.METHODS The cell proliferation was determined by MTT,CCK-8 and colony formation assay.The protein expression was detected by Western blotting.Activity of MMP-2 and MMP-9 was estimated by gelatin zymography.Flow cytometry analysis was used to evaluate the influence of metformin and curcumin on cell cycle arrest and apoptosis,and morphology observation of apoptosis was detected by Hoechst33342.Scratch and transwell assay was performed to detect the cell migration and invasion.The suppression of this combination therapy oncapillary tube formation was detected by tube formation assay.RESULTS Combination of metformin and curcumin induced stronger inhibition on Hep G2 cells proliferation than monotherapywhich related to induction of cell cycle arrest in G2/M phase and apoptosis through regulation of the protein expression of cyclin B and Bcl-2/Bax.Moreover,the co-treatment of metformin with curcumin exerted an enhanced inhibitory effect on Hep G2 cell metastasis and synergistically inhibited the tube formation of HUVEC cells.The suppression of PI3K/AKT/m TOR pathway and inhibition the protein expression of STAT3,MMP9,MMP2 and VEGF might involve in this synergistic effects of combination treatment.CONCLUSION Combination of metformin and curcumin inhibited Hep G2 cells proliferationmore effectively than monotherapy and synergistically induced a greater inhibition on migration and invasion of Hep G2 cells.
