科研之友
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摘要
The poor prognosis of esophageal squamous cell carcinoma (ESCC) emphasizes the urgent need to better understand the carcinogenesis and develop prevention strategies. Previous studies have highlighted the potential of using Vitamin E (tocopherols) for cancer chemoprevention, but the preventive activity of alpha-Tocopherol against ESCC remains to be elucidated. Our data showed that early-stage supplementation with alpha-Tocopherol significantly prevented esophageal carcinogenesis induced by N-nitrosomethylbenzylamine (NMBA) in ESCC rat model. In the Het-1A cell model, alpha-Tocopherol markedly suppressed cell proliferation, promoted cell cycle G2-phase arrest and increased apoptosis. Gene microarray and proteins array analysis indicated that Akt signaling was a potential target for alpha-Tocopherol. We further demonstrated that alpha-Tocopherol increased the expression of PPAR. and its downstream tumor suppressor PTEN. Knockdown of PPAR gamma activated Akt signaling transduction, whereas this process was attenuated by the presence of alpha-Tocopherol and PPAR gamma agonist Rosiglitazone. In contrast, the effect of alpha-Tocopherol on Akt inhibition was not observed in established tumors, neither in cancerous cell lines which constitutively expressed higher levels of PPAR gamma. These results were closely correlated with the ineffectiveness of alpha-Tocopherol in the late stage of ESCC carcinogenesis. Taken together, our study suggested that alpha-Tocopherol may serve as a PPAR gamma agonist for the chemoprevention of esophageal cancer.
