title: A taspine derivative supresses Caco-2 cell growth by competitively targeting EphrinB2 and regulating its pathway.
abstract: Colorectal cancer is a common gastrointestinal malignancy worldwide and it is a lethal and aggressive malignancy with a dismal prognosis. In the present study, we investigated the effect of taspine derivative 12k on human colorectal cancer targeted at EphrinB2 and its PDZ. The results indicated that 12k could bind to EphrinB2 and showed a higher suppressive effect on EphrinB2/HEK293 than on HEK293 cells. Caco‑2 cells were screened for high expression of EphrinB2. We found that 12k not only significantly decreased Caco‑2 cell viability and colony formation but impaired migration. Meanwhile, 12k effectively inhibited blood vessel formation in a tissue model of angiogenesis. Mechanistic studies revealed that 12k significantly reduced the phosphorylation of EphrinB2 and PDZ protein PICK1. Accordingly, it was associated with the downregulation by 12k of the PI3K/AKT/mTOR and MAPK signaling pathways which were downstream of VEGFR2, yet it had no effect on VEGFR3. Moreover, the expression of CD34, CD45 and HIF‑1α were downregulated in the Caco‑2 cells. In conclusion, our findings showed that 12k had an inhibitory effect on the growth of Caco-2 cells, and it functioned by interrupting the phosphorylation of EphrinB2 and its related signaling pathway.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bingling
authors.initials: B
authors.lastname: Dai
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D036388:Ephrin-B2 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000470:Alkaloids; D036388:Ephrin-B2; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; C000601239:EFNB2 protein, human; C546842:MTOR protein, human; C018394:taspine