Abstract
The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of water extracts from ZSP, a Chinese herbal drug, on 7,12-dimethlbenz(a) anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP water extraction on oral carcinogenesis. DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6–8 weeks old) three times per week for 6 weeks in order to induce the development of oral tumors. Then ZSP water fraction is applied topically to the oral tumor lesions at varying dosages (0.35 g/100 ml; 0.7 g/100 ml; 1.4 g/100 ml) to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting. Liver and kidney toxicity were also detected. Average tumor number in each treatment group is lower than positive control group. Moderate-dose group decreased from 2.3 ± 1.8 to 1.5 ± 1.1 (P < 0.05); high-dose group reduced to 1.2 ± 1.0 (P < 0.01). The average tumor volume had not significant difference. It showed that there were no apparent liver and kidney toxicity in the long-term. Topical application of ZSP water fraction also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of mitogen-activated protein kinase (MAPK). In addition, ZSP water fraction promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production. The water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.
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