A low molecular weight polysaccharide isolated from Agaricus blazei Murill (LMPAB) exhibits its anti-metastatic effect by down-regulating metalloproteinase-9 and up-regulating Nm23-H1

• Published in: The American journal of Chinese medicine (1979) Vol. 37; no. 5; p. 909
• Main Authors: Niu, Ying-Cai, Liu, Ji-Cheng, Zhao, Xue-Mei, Cao, Jun
• Format: Journal Article
• Language: English
• Published: Singapore 2009
• Subjects: Agaricus - chemistry; Animals; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immunohistochemistry; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Melanoma, Experimental - pathology; Melanoma, Experimental - prevention & control; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasms, Experimental - pathology; Neoplasms, Experimental - prevention & control; NM23 Nucleoside Diphosphate Kinases - genetics; NM23 Nucleoside Diphosphate Kinases - metabolism; Polysaccharides - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation - drug effects; Xenograft Model Antitumor Assays
• ISSN: 0192-415X
• DOI: 10.1142/s0192415x09007351

The components of Agaricus blazei Murill (AbM) have been shown to possess antitumor potentials. Herein, we attempted to explore the anti-metastatic effect and underlying mechanism of a low molecular weight polysaccharide isolated from AbM (LMPAB). Matrigel invasion assay was applied to evaluate the effect of LMPAB on migration of BEL-7402 hepatic cancer cells in vitro. In vivo, the anti-metastatic effect of LMPAB was investigated in mouse B16 melanoma and a double-grafted SW180 tumor models. mRNA and protein levels of metalloproteinase-9 (MMP-9) or nm23-H1 upon LMPAB treatment were detected by real-time PCR and immunohistochemistry assays. LMPAB significantly reduced the invasion of BEL-7402 cells. In vivo, LMPAB was revealed to decrease lung metastatic foci in mouse B16 melanoma model. In the double-grafted SW180 mouse tumor model, we further demonstrated that intratumoral treatment of LMPAB inhibited the growth of tumor on treated side but also suppresses the regression of metastatic tumors on the non-treated side. Moreover, LMPAB reduced MMP-9 but enhanced nm23-H1 mRNA and protein expression. LMPAB displays anti-metastatic activities, indicating the potential of its clinical application for the prevention and treatment of cancer metastasis. Its anti-metastatic effect may relate to the modulation on MMP-9 and nm23-H1.