Resveratrol enhances anticancer effects of paclitaxel in HepG2 human liver cancer cells.

ABSTRACT

BACKGROUND: The aim of this in vitro study was to measure the enhanced anticancer effects of Res (resveratrol) on PA (paclitaxel) in HepG2 human liver cancer cells. METHODS: The MTT (thiazolyl blue tetrazolium bromide, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), flow cytometry, qPCR (real-time quantitative polymerase chain reaction) and western blot assay were used for cells growth inhibitory effects, cells apoptosis (DNA content of sub-G1), mRNA and protein expressions, respectively. RESULTS: The 10 µg/mL of Res had no growth inhibitory effect on Nthy-ori 3-1 normal cells or HepG2 cancer cells meanwhile the 5 or 10 µg/mL of PA also had no growth inhibitory effect on Nthy-ori 3-1 normal cells. Where as PA-L (5 µg/mL) and PA-H (10 µg/mL) had the growth inhibitory effects in HepG2 cancer cells, and Res increase these growth inhibitory effects. By flow cytometry experiment, after Res (5 µg/mL) + PA-H (10 µg/mL) treatment, the HepG2 cells showed the most apoptosis in cells as compared to other treatments groups, and after additionally treated with Res, both the apoptosis cells of two concentrations PA were raised. As PA raised it also raised the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax (Bcl-2 assaciated X protein), p53, p21, IκB-α (inhibitor of NF-κB alpha), Fas (factor associated suicide), FasL (factor associated suicide ligand), TIMP-1 (tissue inhibitor of metalloproteinases 1), TIMP-2 (tissue inhibitor of metalloproteinases 2) and decrease Bcl-2 (B cell leukemia 2), Bcl-xL (B cell leukemia extra large), HIAP-1 (cIAP-1, cellular inhibitor of apoptosis 1), HIAP-2 (cIAP-2, cellular inhibitor of apoptosis 2), NF-κB (nuclear factor kappa B), COX-2 (cyclooxygenase 2), iNOS (inducible nitric oxide synthase), MMP-2 (metalloproteinase 2), MMP-9 (metalloproteinase 9), EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), Fit-1 (VEGFR-1, vascular endothelial growth factor receptor 1). Meanwhile, the 5 µg/mL of Res could enhance these mRNA expressions changes as compared to the control cells. CONCLUSION: From these results, we can conclude that Res could raise the anticancer effects of PA in HepG2 cells, Res could be used as a good sensitizing agent for PA.