After xenograft transplantation, mice bearing tumors were observed and tumor size was measured once every 3 days with vernier caliper. C, latent membrane protein 1, antibody targeted therapy, nasopharyngeal carcinoma, apoptosis, VEGF 1. Introduction Nasopharyngeal carcinoma (NPC) is a kind of malignant tumor that originates from the epithelium of nasopharynx. During the progress of NPC, early cervical lymph node metastasis and distant metastasis may occur, representing a serious problem [1,2]. Current treatments of NPC are mainly radiotherapy and adjuvant chemotherapy, but the total five year survival rate is FTI 276 less than 40% and a series of side-effects are associated with radiotherapy and chemotherapy. Therefore, it is an urgent need to develop effective and safe therapeutics for NPC [3C5]. The infection with the Epstein-Barr virus (EBV) is one of the most important etiologic factors of NPC. EBV is a prototype gamma herpes virus that infects a large number of the population in the world and contributes to the pathogenesis of many EBV-associated cancers, including cervical carcinoma, gastrointestinal carcinoma and NPC [6,7]. Several latent genes are expressed during EBV infection, such as Epstein-Barr nuclear antigen 1 (EBNA1), Rabbit polyclonal to ABHD3 latent membrane protein FTI 276 1 (LMP1), LMP2A, and EBV-encoded RNAs (EBERs). LMP1 is a protein with unique characteristics and has been suggested as one of the major FTI 276 oncogenic factors by modulating several pathways involved in NPC, such as FTI 276 vascular endothelial growth factor (VEGF) [8]. Moreover, up to now LMP1 is the only latent protein implicated in the modulation of NPC cell differentiation, transformation and malignancy [9]. Consequently, LMP1 is a promising molecular target for NPC therapy. Although several therapeutic antibodies that target oncogenic products of EBV are currently approved for clinical treatment of NPC [10,11], targeted antibody therapy against LMP1 for NPC treatment has not been reported. In our previous study, we screened a humanized anti-LMP1 antibody Fab from a human na?ve Fab phage library but its anti-tumor effect was not characterized [12]. Mitomycin C (MMC) is a classic chemotherapeutics which exhibits effective anti-tumor effects against a variety of solid tumors by inducing apoptosis and reducing drug resistance [13,14]. Notably, the inhibitory effects of MMC against NPC cells have been reported previously [15]. Combination therapy with various drugs is a common strategy in cancer treatment to obtain an additive or synergistic effect and to reduce the potential toxicity. So far, numerous MMC-containing combination remedies have been reported with encouraging clinical effects [16,17]. In this study, we designed a therapy remedy that combined the traditional chemotherapy drug MMC with a novel LMP1 antibody Fab, and evaluated the anti-cancer effects of this new combination therapy in NPC xenograft mice = 6 for group I; = 8 for group IICV). < 0.001 group V; **< 0.05 group III; ***< 0.05 group IV. 2.2. MMC in Combination with Anti-LMP1 Fab Exhibits Synergistic Effect to Induce the Apoptosis of HNE2 Cells 16.6%; < 0.01). In combined therapy, the MMC (2 mg/kg) + Fab (4 mg/kg) treatment group showed a higher percentage of apoptotic cells than the control group (28% 7.87%; < 0.01) and MMC (2 mg/kg) treatment group (28% 16.6%; < 0.01). In addition, in combination therapy with decreased MMC concentration (1 mg/kg) and Fab (4 mg/kg), the percentage of apoptotic cells was still significantly higher than the control group (20.42% 7.87%; < 0.01) and MMC (2 mg/kg) group (20.42% 16.6%; < 0.05) (Figure 2). These results demonstrate that MMC synergized with anti-LMP1 Fab to induce the apoptosis of HNE2 cells < 0.01 group V; ** < 0.01 Group IV; *** < 0.05 group III and IV. 2.3. MMC in Combination with Anti-LMP1 Fab Exhibits Synergistic Effect to Inhibit VEGF Expression in HNE2 Cells Finally we detected VEGF expression in xenografts in nude.