- 期刊
Antitumor Activity of Combination Treatment of Lentinus edodes Mycelium Extracts with 5-Fluorouracil against Human Colon Cancer Cells Xenografted in Nude Mice
並列摘要
AIM: 5-Fluorouracil (5-FU) is one of the widely used chemotherapeutic drugs targeting various cancers, but its chemoresistance remains as a major obstacle in clinical settings. In this study, we evaluated the in vivo efficacy of Lentinus edodes mycelium extracts (designated as LEM), an edible mushroom extracts, as a 5-FU adjuvant agent. Furthermore, we intended to study the underlying mechanisms to account for the role of LEM. METHODS: Human colon cancer COLO 205 cells were treated with 5-FU, LEM, or combination of 5-FU with LEM. Induction of apoptosis and cell cycle arrest was demonstrated by DNA ladder electrophoresis and flow cytometry, respectively. Additionally, COLO 205 cells were transplanted into athymic nude mice as a tumor model for evaluation of the antitumor effect of combination treatment with LEM plus 5-FU. The mechanisms for altered cell cycle progression were investigated by immunoblotting analyses of the G0/G1-phase regulatory proteins. RESULTS: COLO 205 cells were markedly sensitized to apoptosis and G0/G1-phase arrest by combination treatment of 5-FU with LEM when compared with 5-FU alone. Our results furthermore indicated that LEM markedly enhanced the 5-FU-mediated up-regulation of the p53, p21/Cip1 and p27/Kip1 proteins in COLO 205 cells-xenografted tumor tissues. In contrast, although the expression levels of cyclins B and D3 proteins were down regulated in the 5-FU-treated tumor tissues, no significant potentiation effect was observed in the tumors with 5-FU and LEM combination treatment. CONCLUSION: Our results suggest that combination of 5-FU with LEM may represent a novel chemotherapeutic strategy in colon cancers and that p53, p21/Cip1 and p27/Kip1 may play some important roles for the involvement in antitumor activity.
延伸閱讀
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