Experimental Study Of Tea Polyphenol Inhibit Human Nasopharyngeal Carcinoma And Xenograft Growth In Nude Mice

Objective Nasopharyngeal carcinoma(NPC),a mainly composed by poorly differentiated squamous cell carcinoma head and neck malignant tumor,is widely prevalent in Southeast China.So far,the most common and effective treatment of nasopharyngeal carcinoma patients is primarily based on radiotherapy,and concurrent adjuvant chemotherapy can also improve survival rates.Although effective,they can also damage normal cells and cause local or systemic complications which may seriously affect the treatment and quality of life of patients.To enhance radiotherapy and chemotherapy effects as well as reduce damage to normal tissue,it is important for anti-tumor theraping to find natural,efficient and low toxicity plant drugs.Tea polyphenols(TP)are natural polyphenolic compounds containing various chemical constituents extracted from tea.Numerous studies demonstrate tea polyphenols have a variety of bioactive polyphenols,such as anti-cancer,anti-oxidation,anti-mutation,radiation protection,the prevention of cardiovascular disease[1].A large number of epidemiological investigations,animal experiments and experiments in vitro showed tea polyphenols can inhibit tumor formation affect by affecting signal transduction,gene expression,cell cycle and,apoptosis antagonizing tumor angiogenesis etc,but they didn’t damage normal histiocytes.Studies are mostly involved in cell cycle and apoptosis and expression of related apoptotic factor,however,The study of inhibiting tumor growth and metastasis through affecting nasopharyngeal carcinoma angiogenesis is still not well defined at the moment.Our studies identified the inhibitory effects of polyphenols on nasopharyngeal carcinoma cell by HONE1 and the corresponding effect in nude mice and further explore the mechanism of tea polyphenols on nasopharyngeal carcinoma.Methods After treated with different concentration of tea polyphenol,CCK-8 assay,fluorescent staining,cell scratching assay and transwell assay were applied to detect the effect of tea polyphenol on the HONE1 cells.Furthermore,the expression of protein VEGF was investigated by flow cytometry assay.We established the model of subcutaneous tumors in nude mouses by transplanting HONE1 cells.Two experimental groups included low and high dose of TP and control group were designed.The expression of VEGF gene and protein were assessed by real-time PCR and Western Blot.Results It was found that tea polyphenol could inhibit NPC cell proliferation significantly in a dose-dependent manner,however,little impact was observed in normal nasopharyngeal epithelial cell line NP69.Furthermore,it was demonstrated by fluorescent staining assay that tea polyphenol could induce NPC cell apoptosis,and cell scratching assay and transwell assay showed that tea polyphenol could inhibit cell migration and invasion.Compared with the model groups,tea polyphenol can significantly inhibit xenografts growth.Xenografts inhibition rate of low doses of tea polyphenols was 18.82%(P<0.05 while high doses group was 47.66%(P<0.05).Real-time PCR and Western Blot result analysis showed a reduced expression of VEGF as the rising dose of TP(P<0.05).Conclusion Tea polyphenol can significantly inhibit cell proliferation,induce cell apoptosis and decreased the migration and invasion ability of NPC cells in vitro;Tea polyphenol can inhibit the growth of xenografts in nude mice in vivo and the mechanism might be inhibiting angiogenesis.Tea polyphenol might be a tumor suppressor.