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云芝水提取物对小鼠乳腺4T1癌的体内外抗肿瘤及抗转移作用

In vivo and in vitro anti-tumor and anti-metastasis effects of Coriolus versicolor aqueous extract on mouse mammary 4T1 carcinoma.

作者信息

Luo Ke-Wang, Yue Grace Gar-Lee, Ko Chun-Hay, Lee Julia Kin-Ming, Gao Si, Li Long-Fei, Li Gang, Fung Kwok-Pui, Leung Ping-Chung, Lau Clara Bik-San

机构信息

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

出版信息

Phytomedicine. 2014 Jul-Aug;21(8-9):1078-87. doi: 10.1016/j.phymed.2014.04.020. Epub 2014 May 22.

DOI:10.1016/j.phymed.2014.04.020
PMID:24856767
Abstract

Coriolus versicolor (CV), a medicinal mushroom widely consumed in Asian countries, has been demonstrated to be effective in stimulation of immune system and inhibition of tumor growth. The present study aimed to investigate the anti-tumor and anti-metastasis effects of CV aqueous extract in mouse mammary carcinoma 4T1 cells and in 4T1-tumor bearing mouse model. Our results showed that CV aqueous extract (0.125-2 mg/ml) did not inhibit 4T1 cell proliferation while the non-cytotoxic dose of CV extract (1-2 mg/ml) significantly inhibited cell migration and invasion (p<0.05). Besides, the enzyme activities and protein levels of MMP-9 were suppressed by CV extract significantly. Animal studies showed that CV aqueous extract (1 g/kg, orally-fed daily for 4 weeks) was effective in decreasing the tumor weight by 36%, and decreased the lung metastasis by 70.8% against untreated control. Besides, micro-CT analysis of the tumor-bearing mice tibias indicated that CV extract was effective in bone protection against breast cancer-induced bone destruction as the bone volume was significantly increased. On the other hand, CV aqueous extract treatments resulted in remarkable immunomodulatory effects, which was reflected by the augmentation of IL-2, 6, 12, TNF-α and IFN-γ productions from the spleen lymphocytes of CV-treated tumor-bearing mice. In conclusion, our results demonstrated for the first time that the CV aqueous extract exhibited anti-tumor, anti-metastasis and immunomodulation effects in metastatic breast cancer mouse model, and could protect the bone from breast cancer-induced bone destruction. These findings provided scientific evidences for the clinical application of CV aqueous extract in breast cancer patients.

摘要

云芝,一种在亚洲国家被广泛食用的药用真菌,已被证明在刺激免疫系统和抑制肿瘤生长方面有效。本研究旨在探讨云芝水提取物对小鼠乳腺癌4T1细胞和4T1荷瘤小鼠模型的抗肿瘤和抗转移作用。我们的结果表明,云芝水提取物(0.125 - 2 mg/ml)不抑制4T1细胞增殖,而无细胞毒性剂量的云芝提取物(1 - 2 mg/ml)显著抑制细胞迁移和侵袭(p<0.05)。此外,云芝提取物显著抑制MMP - 9的酶活性和蛋白水平。动物研究表明,云芝水提取物(1 g/kg,每日口服4周)可有效降低肿瘤重量36%,并使肺转移减少70.8%,与未处理的对照组相比。此外,对荷瘤小鼠胫骨的微型CT分析表明,云芝提取物对乳腺癌诱导的骨破坏具有有效的骨保护作用,因为骨体积显著增加。另一方面,云芝水提取物处理产生了显著的免疫调节作用,这体现在经云芝处理的荷瘤小鼠脾脏淋巴细胞中IL - 2、6、12、TNF -α和IFN -γ产生的增加。总之,我们的结果首次证明云芝水提取物在转移性乳腺癌小鼠模型中具有抗肿瘤、抗转移和免疫调节作用,并能保护骨骼免受乳腺癌诱导的骨破坏。这些发现为云芝水提取物在乳腺癌患者中的临床应用提供了科学依据。

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