Adenovirus-mediated RNA interference targeting FOXM1 transcription factor suppresses cell proliferation and tumor growth of nasopharyngeal carcinoma

Background The Forkhead Box M1 (FOXM1) transcription factor, which regulates the expression of genes essential for cell proliferation and transformation, is implicated in tumorigenesis and tumor progression. FOXM1 has attracted much attention as a potential target for the prevention and/or therapeutic intervention in human carcinomas. Methods The levels of FOXM1 expression in clinical tissue specimens and cell lines of human malignant nasopharyngeal carcinoma (NPC) were measured. Knockdown of FOXM1 expression was performed by small interfering RNA in NPC cells. An adenovirus vector (named AdFOXM1shRNA) was constructed to express a short hairpin RNA specific to FOXM1. The efficacy of AdFOXM1shRNA for tumor gene therapy in NPC cells and an in vivo NPC grafting model was assessed. Results A strong expression of FOXM1 was observed in clinical tissue specimens and cell lines of human NPC. Knockdown of FOXM1 expression by FOXM1 specific small interfering RNA diminished the NPC cell proliferation. The infection of AdFOXM1shRNA in NPC cells resulted in the knockdown of FOXM1 mRNA and protein levels, correlated with the reduction of proliferation and anchorage-independent growth of the cancer cells. The growth of NPC tumors was significantly suppressed when inoculated mice were injected with AdFOXM1shRNA in the tumor. Conclusions Together, our results suggest that FOXM1 is a potential therapeutic target for NPC and AdFOXM1shRNA may be an additional gene therapeutic intervention to be evaluated in future treatment strategies for patients with NPC. Copyright (C) 2012 John Wiley & Sons, Ltd.