茶黄素TF-3通过67LR调控PKCδ/aSMase通路诱导前列腺癌PC-3细胞凋亡的机制研究

前列腺癌发病率为西方国家男性肿瘤之首。我国前列腺癌发病死亡率逐年增长，对前列腺癌的防治及其机制研究十分必要。研究表明，绿茶EGCG对前列腺癌具有显著抑制作用，茶黄素单体TF-3是绿茶EGCG衍生物，具有EGCG所有活性位点，对某些癌症抗性优于EGCG。我们前期研究证实，茶黄素TF-3能够显著诱导前列腺癌PC-3细胞凋亡，促进PC-3细胞中PKCδ（Ser664）磷酸化，上调aSMase蛋白表达，其抑制细胞生长能力与67LR表达水平显著相关。由此推测“TF-3通过与67LR作用激活PKCδ/aSMase信号通路，进而诱导PC-3细胞凋亡”。本研究拟以前列腺癌PC-3细胞为模型，阐明TF-3调控PKCδ/aSMase信号通路诱导PC-3细胞凋亡，明确67LR的介导作用，揭示TF-3诱导前列腺癌PC-3细胞凋亡的机制，最后在前列腺癌小鼠模型中验证，为红茶及其功能成分抗癌机制研究提供理论依据。

Prostate cancer (PC) is the most common invasive malignancy among human males in the western world. In recent years, the morbidity and mortality rate of prostate cancer have rising tendency in our country. Therefore, the prevention of prostate cancer and its pathogenesis research have great significance. There is increasing evidence revealing that green tea EGCG showed significant inhibition to the growth of prostate cancer cells. Theaflavins monomer TF-3 is EGCG derivatives, contains all active site of EGCG, having stronger resistance for certain types of cancer than EGCG. Our previous study confirmed that TF-3 have significant effects of anti-prostate cancer and induce apoptosis of PC-3 cells. We also found that TF-3 can raised aSMase protein expression and protein kinase C δ (PKCδ) phosphorylation at Ser664. Moreover, the inhibitory activity was correlated with expression of 67LR. Thus, we speculate that “the mechanism by which TF-3 induces apoptosis may be dependent on the PKCδ/aSMase signaling pathway via 67LR functions as a cancer-specific death receptor”. In this project, by using prostate cancer PC-3 cells as a model, we clarified TF-3 induced apoptosis of prostate cancer PC-3 cells through PKC δ/aSMase signaling pathways, and cleared the mediating role of 67LR in this process, revealing the mechanism of TF-3 induced PC-3 apoptosis and validating this mechanism in prostate cancer mice model. Further research may provide us with more information about the anti-cancer activities of black tea and its functional components and facilitate the usage in cancer prevention and treatment.