Vitamin E Analog α-TEA and Celecoxib Alone and Together Reduce Human MDA-MB-435-FL-GFP Breast Cancer Burden and Metastasis in Nude Mice
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- Zhang, S., Lawson, K.A., Simmons-Menchaca, M. et al. Breast Cancer Res Treat (2004) 87: 111. doi:10.1023/B:BREA.0000041593.69178.57
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α-TEA, a nonhydrolyzable ether analog of vitamin E (RRR-α-tocopherol), and celecoxib, a specific COX-2 inhibitor, were delivered separately or in combination to investigate their anticancer properties, using MDA-MB-435-FL-GFP human breast cancer xenografts in nude mice. Liposomal formulated α-TEA administered as an aerosol and celecoxib fed at 500 or 1250 mg/kg diet for 31 days separately or in combination significantly reduced tumor volume in comparison to control (p < 0.001 for all treatment groups). Of special note, the combinations of α-TEA + celecoxib (1250) inhibited tumor volume significantly better than either single treatment (p < 0.001 and p < 0.001). Average number of macroscopic lung metastases were significantly reduced in all treatment groups in comparison to control, with the exception of celecoxib (500). Mean numbers of microscopic lung and lymph node metastases in all treatment groups were significantly lower than control. Furthermore, the mean number of microscopic lung metastases in the α-TEA+celecoxib (1250) group were significantly lower than either separate treatment. Analyses of 5 μm tumor sections showed that all treatments, with the exception of celecoxib (500) alone, significantly enhanced apoptosis (TUNEL) and significantly decreased cell proliferation (Ki-67). α-TEA and α-TEA + celecoxib (1250) treatments significantly reduced blood vessel density (CD-31) in comparison to control. These data show promise for combination α-TEA + celecoxib chemotherapy for breast cancer.