J. Cancer Mol. 3: 15-22, 2007
[Research Paper]
Antitumor Activity of Combination Treatment of Lentinus edodes
Mycelium Extracts with 5-Fluorouracil against Human Colon Cancer Cells
Xenografted in Nude Mice
Chih-Hsiung Wu, Chi-Chen Wu, and Yuan-Soon Ho1
Departments of Surgery [C.-H. Wu] and Anesthesiology [C.-C. Wu],
School of Medicine, Taipei Medical University and Hospital, Taipei,
Taiwan; Graduate Institute of Biomedical Technology, Taipei Medical
University, Taipei, Taiwan [Y.-S. Ho]
Abstract:
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.
(Keywords: 5-fluorouracil; Lentinus
edodes mycelium extracts; G0/G1 arrest;
apoptosis; p53)
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