Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma.
Proteoglycan (P1) purified from Phellinus linteus has been reported to have anti-disease activities. The objectives of our research were to determine the anti-tumor effect and possible mechanisms of P1 on human cancer cells. Cell inhibition assay showed that P1 has an antiproliferative effect on HepG2, HT-29, NCI-H 460 and MCF-7 human colon cancer cells, especially it was very effective in inhibiting HT-29 cells. When HT-29-bearing mice were treated with P1(100mg/kg), there was relative increase in spleen and thymus weights, the plasmatic pIgR and IgA levels were significantly increased, also there was a notable decrease in plasmatic PGE2, Reg IV, EGFR and Akt concentrations measured by ELISA. RT-PCR analysis suggested that P1-induced HT-29 apoptosis appeared to be associated with a decrease in the levels of expression of Reg IV and EGFR. These results suggest that P1 might have two potential roles in treating cancer; it acts as an immunopotentiator partly through protecting T cells from escaping PGE2 attack and enhancing the mucosal IgA response, and as a direct inhibitor by disrupting the Reg IV/EGFR/Akt signaling pathway.
Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China.
You-Gui
YG
Li
Dong-Feng
DF
Ji
Shi
S
Zhong
Jian-Xun
JX
Zhu
Shi
S
Chen
Gui-Yan
GY
Hu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053487:DEAD-box RNA Helicases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology* / Q000633:toxicity; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000235:genetics; D000073718:Pancreatitis-Associated Proteins; D011458:Prostaglandins E / Q000097:blood; D011509:Proteoglycans / Q000494:pharmacology* / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D007070:Immunoglobulin A; D007155:Immunologic Factors; D037181:Lectins, C-Type; D009687:Nuclear Proteins; D000073718:Pancreatitis-Associated Proteins; D011458:Prostaglandins E; D011509:Proteoglycans; C428528:REG4 protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; C466365:DHX32 protein, human; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D053487:DEAD-box RNA Helicases