Induction of Apoptosis in Head and Neck Cancer Cells by Dominant Negative C-myb Gene Therapy / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Although the role of c-myb in head and neck tumor has not been studied, aberrant expression of c-myb in various cancer has been demonstrated recently, suggesting that c-myb may play a role in tumorigenesis. Consequently, disrupting c-myb function might prove a possible stratergy for controlling cancer cell growth. The purpose of this study is to investigate the possibility of clinical application of adenovirus-mediated dominant negative c-myb (DN-myb) gene therapy in head and neck cancer. MATERIALS AND METHOD: All tissues were obtained from patients undergoing therapeutic operation for head and neck tumors and were assayed the expression of c-myb and bcl-2 in tumor and normal tissue by RT-PCR. We have generated a replication-deficient recombinant adenovirus encoding the dominant negative c-myb (Ad/DN-myb) or control adenovirus encoding no transgene (Ad/GFP) and infected adenovirus to SNU-1076, head and neck tumor cell line. We examined cell proliferation by 3H-thymidine assay, apoptosis by DNA fragmentation, bcl-2 expression and Akt/PKB phosphorylation by Western immunoblot, and IGF-II, VEGF mRNA expression by RT-PCR. RESULTS: c-myb expression of head and neck tumor tissues was significantly higher than that of normal tissue, indicating that these genes may play an important role in carcinogenesis of head and neck tumor. Ad/DN-myb infected SNU-1076 cells decreased cell proliferation, IGF-1I and VEGF expression, and remarkably increased their apoptosis through the down-regulation of bcl-2 expression and the inhibition of Akt/PKB pathway activation. CONCLUSION: Results obtains from these study suggest that DN-myb induced apoptosis of head and neck tumor cells and the adenovirusmediated DN-myb gene therapy may be a potential molecular therapy for the treatment of head and neck tumor.