Evaluation of Cyclooxygenase-2, P53, Vascular Endothelial Growth Factor, and Nitric Oxide Synthase-2 in Angiogenesis and Growth of Tobacco-Related Malignancies

Introduction In India, tobacco consumption is responsible for half of all the cancers in men and a quarter in women. The present study focuses on the expression of cyclooxygenase-2 (COX-2), P53, vascular endothelial growth factor (VEGF), and nitric oxide synthase (NOS) and their relationship with the growth and angiogenesis of tobacco-related malignancies of the oral cavity, esophagus, lungs, and stomach. It further evaluates the carcinogenic action of nicotine and examines whether COX-2 and NOS-2 overexpression is responsible for tumor growth and associated angiogenic VEGF expression via its receptor.Material and Methods A cross-sectional study on 140 biopsies, resected specimens of cancer of oral cavity, esophagus, stomach, and lungs, was done. Immunohistochemical evaluation for p53, COX-2, VEGF, and inducible NOS was done. Relevant statistical analysis was applied for the significance of the findings.Results Immunohistochemical evaluation of pattern of expression of COX-2, NOS-2, VEGF, and p53 was done in both tobacco- and nontobacco-associated cases. The results of the present study revealed an upregulation of COX-2, NOS-2, VEGF, and p53 in all the malignancies.Conclusion The present results indicated that p53 protein accumulation and increased expression of COX-2, NOS-2, and VEGF might be responsible for carcinogenesis and tumor aggressiveness by enhancing angiogenesis. A possible significant effect of nicotine on COX-2 and P53 expression in tumorigenesis is revealed. These data might have important implications for the therapeutic use of COX-2, NOS-2, and VEGF inhibitors as well as of p53 gene therapy in future anticancer therapeutic strategies in tobacco-related malignancies.