The Effect of Meloxicam on Tumor Growth and Angiogenesis of Human Gatric Cancer Cell Line Xenograft in Nude Mice

ABSTRACT

PURPOSE: In general, tumor growth is dependent on angiogenesis. COX, known as modulator of angiogenesis, consists of two at least isozymes constitutive COX-1 and stress- induced COX-2. The latter is known in case of gastric cancer to be overexpressed in neoplastic tissue but not in adjacent normal tissue. To clarify the effect of COX-2 inhibitors on tumor growth and angiogenesis, we investigated the effects of Meloxicam (a selective COX-2 inhibitor) on gastric cancer xenograft in nude mise that overexpress COX-2. METHODS: MKN45 gastric cancer cell lines that overexpress COX-2 were inoculated subcutaneously into athymic mice. The mean tumor volume, apoptotic index, proliferative index, microvessel count and angiogenic factors (VEGF and bFGF) were measured in the control group (12 cases) and the meloxicam treated group (23 cases). RESULTS: There was no significant difference of COX-2 expression between the control and meloxicam treated groups in mRNA level as measured by RT-PCR, nor in protein level by Western blotting. However, in the meloxicam treated group, apoptosis was increased to a statistically significant degree (P<0.01) while the proliferation index as measured by Ki-67, the mean tumor volume and angiogenesis were all significantly decreased, as compared with the control group (P<0.01). CONCLUSION: The possible suppression of angiogenesis and tumor growth in gastric cancer xenograft by meloxicam suggests potentially. Novel and promising applications of COX-2 inhibitors in the adjuvant treatment of gastric cancer. However, further clinical study will be needed to determine its efficacy in such treatment modalities.