Inhibitory Effect And The Mechanism Of Mitomycin C On Human Nasopharyngeal Carcinoma Cell Line Hne2,hne2/lmp-1

Nasopharyngeal carcinoma (Nasopharyngeal Carcinoma, NPC) is a nasopharyngeal epithelial malignant tumor with high incidence in our country, which is sensitive to radiotherapy and chemotherapy. In the past, the main treatment is radiotherapy, but poor for terminally patients. Recently, Induction chemotherapy and concurrent radiotherapy with chemotherapy can control distant metastasis and local Recurrence, which has become a comprehensive treatment of nasopharyngeal carcinoma.Mitomycin C (mitomycin C, MMC) is an anti-tumor antibiotic, which is effective against a variety of solid tumors. It has been used for clinical treatment of a variety of tumors. Its mechanism is to undermine the structure of DNA and RNA, causing cell apoptosis. Caspases family, Bcl-2 family, p53 and many other factors are involved in MMC-induced apoptosis. Caspase family is the most important one of the implementation of cell apoptosis, the activation of Caspase-3 will enable many proteins or kinase of cell structure, cell cycle and DNA repair-related inactivation, and induce apoptosis.Objective:EBV-latent membrane protein 1 have a variety function to signal transduction pathways through different signal amplification and a large number of gene expression, thereby enhancing the viability of cells, adhesion the capacity of invasion and angiogenesis ability to participate in the occurrence of nasopharyngeal cancer, development and transferation. Methods:Human nasopharyngeal carcinoma cell line HNE2,HNE2/LMP-1 were treated with different concentrations of MMC; the culture medium served as controls. The growth inhibition rate of HNE2 and HNE2/LMP-1cells were examined by MTS assay; the morphological changes of cells were observed under fluorescence microscope; caspase-3 activity was assessed by colorimetry; and the cell cycle and apoptosis were detected by flow -cytometry.Results:MMC inhibited the growth of HNE2 HNE2/LMP-1 cells in a time and dose dependent manner, with maximal inhibitory rate about (79.01±5.32)% and (76.45±4.36)%. The IC50 after 24h were about 19μg/ml and 28μg/ml respectively. After MMC treatmen, the amount of suspended cell increased and the cells shrank, rounded and smashed, with particle like substance found in the cells. The most obvious changes were found at 48 h after treatment with 40μg/ml MMC. Besides, the Caspase-3 activities were up-regulated by MMC in HNE2,HNE2/LMP-1cells in a time and concentration dependent manner. Flow cytometry detection revealed that MMC induced apoptosis rather than the cell cycles of HNE2 and HNE2/LMP-1cells. Statistics show that growth inhibition rate is difference between HNE2 and HNE2/LMP-1 cell lines after MMC treatment.Conclusion:MitomycinC obviously inhibit the growth of human nasopharyngeal carcinoma cells, possibly by activating Caspase-3 and inducing cell apoptosis. The datas suggest that LMP1 can promote HNE2 cell growth and against apoptosis.