期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 240, 期 12, 页码 1672-1681出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370215573396
关键词
Resveratrol; 5-fluorouracil; synergistic effect; S-phase arrest; two-stage mouse skin carcinogenesis
资金
- Hebei Education Department [Z2011163]
- natural science foundation of Hebei Province [H2013206147]
- National Natural Science Foundation of China [81201642]
Many studies have shown that natural dietary agents, in combination with chemical agents, can improve the therapeutic response of cancers to chemotherapy and reduce the associated side-effects. In the present study, we investigated the therapeutic potential and mechanisms of anticancer effects for the combination of 5-fluorouracil (5-FU) and resveratrol (Res). In these studies, we employed the cancer cell lines TE-1 and A431 and an animal model of skin cancer. The presented results provide the first evidence that Res can enhance the anti-tumor potency of 5-FU by inducing S-phase arrest. The combination of Res and 5-FU demonstrates synergistic efficacy, causing tumor regression in a two-stage model of mouse skin carcinogenesis induced by DMBA and TPA. There was clear evidence of Res augmenting the growth inhibitory effect of 5-FU on the TE-1 and A431 cancer cells invitro. In the invivo studies, the tumor regression rate in the combination group increased significantly after four weeks of treatment (P<0.01). The combination of 5-FU and Res significantly increased the percentage of apoptotic cells and the level of activated caspase-3, cleaved PARP and p53 proteins as well as increased the Bax/Bcl-2 ratio. In conclusion, the 5-FU/Res combination enabled a more effective inhibition of cell growth and the induction of apoptosis in cancer cells than 5-FU alone. The results of this study suggest that chemotherapy using natural dietary agents with chemical agents represents a superior cancer treatment option.
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