Discoidin domain receptor 2 (DDR2), a tyrosine kinase receptor belonging to DDRs family, is associated with progression of various cancers. Studies have indicated that DDR2 expression is upregulated in various cancer tissues, which could promote tumors proliferation, invasion, and metastases. Furthermore, patients with high DDR2 expression showed poor 5-year overall survival rate. In addition, DDR2 point mutation can enhance the sensitivity of tumor cells to small molecule tyrosine kinase inhibitor dasatinib, which suggests that DDR2 mutation may be a promising target for cancer therapy.

Objective To investigate the effects and signal transduction pathway of vasonatrin peptide(VNP),a novel man-made natriuretic peptide,on hepatic fibrosis.Methods Mice were injec ted with carbon tetrachloride(CCl4)for 12 weeks,with or without VNP treatment in the last 6 weeks.HE staining and Sirius red staining were performed to evaluate the status of hepatic fibrosis.In vitro after treatment of VNP,and DNA and collagen synthesis of cultured HSC-T6 hepatic stellate cells were assessed by[3H]-thymidine and[3H]proline incorporation,respectively.The signaling pathway involved was identified by radioimmunoassay to detect the levels of intracellular cGMP,and by mimicking experiments using 8-br-cGMP(a membrane-permeable cGMP analog).Blocking experi ments were performed using HS-142-1,an antagonist of guanylyl cyclase-coupled natriuretic peptide receptor(NPR),or KT-5823,the cGMP-dependent protein kinase(PKG)inhibitor.Results VNP markedly alleviated CCl4-induced liver fibrosis in mice.In vitro,HSC-T6 cells demonstrated a dosedependent reduction of DNA and collagen synthesis in the presence of VNP.In addition,VNP significantly increased intracellular levels of cGMP.The effects of VNP were mimicked by 8-br-cGMP,but they were inhibited by HS-142-1,or KT-5823.Conclusion VNP ameliorated liver fibrosis by inhibiting collagen production from hepatic stellate cells via guanylyl cyclase-coupled NPR/cGMP/PKG signal pathway,indicating that VNP might be a new effective agent in the treatment of liver fibrosis.

Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) is a polyphenolic compound primarily found in blueberries, grapes, and a tree wood, pterocarpus marsupium. Studies demonstrate that pterostilbene inhibits a variety of cancers, such as lung, breast, stomach, colon, etc. The anti-cancer activities are related to the regulation of several hallmarks of cancer. Moreover, pterostilbene exhibits much greater bioavailability and bioactivity than resveratrol which warrants further investigation in the anti-cancer functions and mechanisms.
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Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Plant Extracts ; chemistry ; pharmacology ; Stilbenes ; chemistry ; pharmacology