Experimental Study On Anti-tumor Activity By Ad-OSM For Nasopharyngeal Carcinoma

Background and Objective:The incidence of Nasopharyngeal carcinoma (NPC) in southern China, Vietnam,the Philippines and other Southeast Asian region is high.Such as in Chinese Guan-gdong, Guangxi, Fujian province, the incidence is as high as30/100000～50/100000.The adjusted mortality rate is respectively for6.47/100000,4.92/100000,3.28/100000, also occupies the world first place. Nasopharyngeal carcinoma (NPC) morbidityand mortality are along with the increase age. The occurrence and development ofthe nasopharyngeal carcinoma (NPC) is an extremely complex process with manyfactors and genes involved. Gene therapy is a kind of curative treatment with extre-me efficiency, specificity, yet attract more and more attentions, the gene therapy isprobably one of the effective means to cure nasopharyngeal carcinoma (NPC). Rec-ent years, studies have found that OSM gene can inhibit tumor cell growth and i-nduce apoptosis. The experiment intend to use the adenovirus-mediated OSM expre-ssion, to observe the inhibiting effect on the nasopharyngeal carcinoma cells and th-e the tumor-bearing athymic nude mice, and to discuss its possible mechanism.Methods:The CNE-2Z nasopharyngeal carcinoma cells were infected with Ad-OSM, Theexpression of OSM gene in CNE-2Z nasopharyngeal carcinoma cells infected withAd-OSM were detected by RT-PCR and Western blot. The in vitro growth-suppressi-ng, apoptosis-inducing, cell-cycle alteration, apoptosis effect compared with PBS gr-oup, Ad-GFP group in CNE-2Z human nasopharyngeal carcinoma cells were assesse-d by MTT assay, FCM and semi-quantitative RT-PCR was used to detected the tra-nscription of P21, P27, Bcl-2, Survivin genes; and its in vivo anti-tumor effect onnasopharyngeal carcinoma was further observed using CNE-2Z human nasopharynge-al carcinoma transplanted tumor in athymic nude mouse model. The expression of c-ellcycle and apoptosis-and angiogenesis-related proteins (P21, P27, Cox-2, Bcl-2, S -urvivin, Bax, Caspase-3) in CNE-2Z human nasopharyngeal carcinoma and CNE-2Ztransplanted tumor was determined by immunohistochemistry analysis.Results:OSM mediated by adenovirus were proved successful transcribed and translatedin CNE-2Z cells by RT-PCR and Western blot; Adenovirus-mediated OSM signific-antly inhibited CNE-2Z nasopharyngeal carcinioma cell growth, induced cell apoptos-is, and retarded CNE-2Z nasopharyngeal carcinioma transplanted tumor growth in a-thymic nude mouse, exhibiting anti-tumor effect.Ad-OSM can obviously induce G1phase arrest and cell apoptosis of CNE-2Z. Ad-OSM had more marked effect in up-regulating the expression of P21, P27, P53, Bax and Caspase-3and down-regulati-ng the expression of Cox-2, Bcl-2and Survivin.Conclusions:1. Ad-OSM can suppresss tatistically CNE-2Z cells and their xenografts growth innude mice and induced apoptosis (P<0.05).2. Ad-OSM can upregulate the expression P21, P27, P53, Bax, Bcl-2, reduce theexpression of Bcl-2, Survivin, Cox-2, followed by the activation of Caspase-3leading toapoptosis via intrinsic apoptotic pathways in vitro and in vivo.