FOXO3A Drives Proliferation And Apoptosis Through PI3K/AKT Signaling Pathway In Human Nasopharyngeal Carcinoma Cne-1and Cne-2Cells

Background:NPC (nasopharyngeal carcinoma) is one of the most common carcinomas in South China and Southeast Asia with prominent geographic and racial distributions worldwide, due to its characteristics of high degree of malignancy, early metastasis, most of nasopharyngeal carcinoma patients had lymph node metastasis at the time of diagnosis. FoxO3a (Forkhead homeobox type O3a, FKHRL1) is a member of the Forkhead transcription factor superfamily and involved in numerous signaling pathways and plays critical roles in a quantity of physiological and pathological processes, including apoptosis, cell cycle arrest, DNA damage repair, stress resistance. As we known, FoxO3a is identified as a tumor suppressor, and is closely related to in tumorigenesis and cancer progression, many chemotherapy drugs paly a role in the inhibition of tumor growth by FoxO3a. According to our previous study showed that FOX03a as a positive prognostic factor for NPC, as it was lower expression in NPC tissues compared with in normal nasopharyngeal tissues. The aim of this study was to examine the effects of PI3K/Akt/FoxO3a signaling pathway on cell proliferation and apoptosis of human nasopharyngeal carcinoma CNE-1、CNE-2cell lines.Objective:Human nasopharyngeal carcinoma CNE-1、CNE-2cell lines were used as object. To evaluate the effects of FoxO3a activation on proliferation and apoptosis through PI3K/Akt pathway in human nasopharyngeal carcinoma CNE-1and CNE-2cell lines.Methods:Western blot was used to test the protein expression of FoxO3a and P-Akt, Immunofluorescence staining was used to test the subcellular localization of FoxO3a in nasopharyngeal carcinoma CNE-1and CNE-2cells in vitro. Real-time Quantitative PCR was used to measure the mRNA level of FOXO3a in NPC cells. MTT assay and flow cytometry were used to investigate the effects of proliferation and apoptosis on CNE-1and CNE-2cells.Results:The results showed the protein expression and mRNA level of FoxO3a was increased by using PI3K inhibitor LY294002in both cell lines(P<0.05), and the nuclear accumulation of FoxO3a was increased significantly in CNE-1cells(P=0.004) and CNE-2cells(P=0.001). And the activation of FoxO3a could inhibit cell proliferation(P<0.05) and promote apoptosis (P<0.01)in CNE-1and CNE-2cells.Conclusion:PI3K/Akt pathway inhibition could upregulate the expression of FoxO3a, inhibit cell proliferation and induce apoptosis of CNE-1and CNE-2cells, possibly through the regulation of FoxO3a expression.