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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Lijun Sun, Beicheng Deng, Lei Hu, Jialiang Cheng, Tao Xu, Hanmei |
| Description | Author Affiliation: Hu J ( Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.); Cheng T ( Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.); Zhang L ( Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.); Sun B ( Liver Transplant Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.); Deng L ( Liver Transplant Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.); Xu H ( Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.) |
| Abstract | The anti-tumor peptide AP25 is a prototype integrin antagonist, which exhibits antiangiogenic and antitumor activity. The molecular mechanisms by which AP25 inhibits the growth of the MGC803 gastric carcinoma cell line were investigated in the present study. Kras specific RNA interference by lentiviral infection was successfully induced in MGC803 cells [MGC803 short hairpin (sh)RNA group] and the expression levels of Kras, phosphorylated extracellular signalregulated kinase (p-ERK) and cyclin D1 were observed to be markedly decreased. By contrast, AP25 caused cell cycle arrest of intact MGC803 cells and decreased pERK and cyclin D1 expression levels. Of note, 0.43.2 µM AP25 no longer inhibited MGC803 shRNA growth, indicating that AP25, at such concentrations, exerts its effect mainly through the Ras/Raf/mitogen-activated protein kinase kinase/ERK pathway, whereas at 25 µM, AP25 was able to inhibit MGC803 shRNA growth. Chemical inhibitors of Src, cJun Nterminal kinase (JNK) and phosphoinositide 3kinase (PI3K) were used to confirm that 25 µM AP25 inhibited growth of cells in the MGC803 shRNA group and activated intracellular signaling pathways with Src, JNK and PI3K as key enzymes. In conclusion, the present study revealed the signal transduction pathways activated by AP25 at low (0.43.2 µM) or high (25 µM) concentrations. It also confirmed that integrins, when interacting with the freely moving ligand AP25 instead of immobilized extracellular matrix glycoproteins, are able to initiate cell signaling via similar pathways as in the latter case but with a reversed effect, to inhibit cell growth. |
| ISSN | 17912997 |
| e-ISSN | 17913004 |
| Journal | Molecular Medicine Reports |
| Issue Number | 3 |
| Volume Number | 12 |
| Language | English |
| Publisher | Spandidos Publications |
| Publisher Date | 2015-09-01 |
| Publisher Place | Greece |
| Access Restriction | Open |
| Subject Keyword | Angiogenesis Inhibitors Pharmacology Cell Proliferation Drug Effects Cyclin D1 Metabolism Endostatins Gene Expression Peptide Fragments Cell Line, Tumor Genetics Drug Screening Assays, Antitumor Extracellular Signal-regulated Map Kinases Hek293 Cells Jnk Mitogen-activated Protein Kinases Map Kinase Signaling System Phosphatidylinositol 3-kinases Src-family Kinases Research Support, Non-u.s. Gov't Discipline Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Biochemistry Molecular Biology Cancer Research Molecular Medicine Oncology |
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