Serum amyloid A mediates the inhibitory effect of Ganoderma lucidum polysaccharides on tumor cell adhesion to endothelial cells.
Ganoderma ludicum polysaccharides (GlPS) are the major bioactive composition of Ganoderma lucidum, a well-recognized oriental medical fungus. The published data have shown a complementary effect of GlPS in cancer therapy. The present study was designed to determine the anti-tumor efficacy of GlPS and the possible mechanism covering this effect. Murine Sarcoma 180 (S180) model was established, and GlPS administered orally for 10 days. On the 10th day, tumors were weighed to assess the inhibitory effect of GlPS and sera were collected for proteomic analysis and in vitro study. The in vivo results demonstrated that 25, 50 and 100 mg/kg GlPS inhibited S180 growth by 32.67, 44.80 and 45.24%, respectively (P<0.01). Proteomic study revealed marked protein changes after the process of treatment. Three significantly changed proteins were identified by ESI-Q-TOF-MS and database search indicated that they were haptoblobin, apolipoprotein A-II and serum amyloid A (SAA), respectively. Additionally, the expression change of SAA was confirmed by both Western blot and RT-PCR. The adhesion assay showed that GlPS-treated sera dramatically inhibited the adhesion ability of human prostate carcinoma (PC-3M) cells to human umbilical cord vascular endothelial cells (HUVECs), and this effect partially recovered after immunodepletion by the antibody against SAA. Collectively, these results suggest that GlPS inhibited the tumor growth and tumor cell adhesion to HUVECs via up-regulation of SAA protein expression.
Li
Ying-Bo
YB
Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
Wang
Rui
R
Wu
Hong-Li
HL
Li
Yu-Hua
YH
Zhong
Li-Jun
LJ
Yu
He-Ming
HM
Li
Xue-Jun
XJ
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000685:Serum Amyloid A Protein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D011134:Polysaccharides; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein