title: Antitumor effects of Dasatinib on laryngeal squamous cell carcinoma in vivo and in vitro.
abstract: A novel drug named Dasatinib is a highly potent ATP-competitive orally active dual Src/Abl kinase inhibitor with anti-proliferative activity against solid tumors and CML (chronic myeloid leukaemia) cell lines. Dasatinib has been shown to have preclinical activity against human prostate, breast, pancreatic, lung, and head and neck cancer. To determine whether Dasatinib can inhibit the growth of laryngeal squamous cell carcinoma, in the present study, we investigated the antitumor effect of Dasatinib on Hep-2 cells. Hep-2 cells were treated with different concentrations of Dasatinib for different time. Cell proliferation, cell cycle distribution, and cell apoptosis were evaluated using MTT assay, flow cytometry, and fluorescent microscopy. It was found that Dasatinib exhibited significant efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction in a dose- and time-dependent manner. Measuring the modulation of regulators in the cell cycle, apoptosis and signal transductions by western blot analysis showed that the effect of Dasatinib was due to suppression of the expression of Bax, Bcl-2, Caspase-3, and Caspase-8. Moreover, in vivo studies were performed in a nude mouse xenograft model, the new prescription (DDP + Dasatinib) was better than DDP alone in terms of therapeutic efficacy. In conclusion, the antitumor effect of Dasatinib on Hep-2 cells was due to the induction of cell cycle arrest as well as apoptosis. The possible mechanisms underlying the action might be attributed to the suppression of Src phosphorylation. This investigation suggests a potential clinical application of Dasatinib for the treatment of laryngeal cancer patients.
authors: Department of Otolaryngology, Sheng-Jing Hospital, China Medical University, 110004 Shenyang, People Republic China.
authors: Yan
authors: Y
authors: Song
authors: Xin
authors: X
authors: Sun
authors: Wei-Liang
authors: WL
authors: Bai
authors: Wen-Yue
authors: WY
authors: Ji
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D000069439:Dasatinib; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007822:Laryngeal Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D002945:Cisplatin; D000069439:Dasatinib
references: Lancet Oncol. 2001 May;2(5):261-9
references: 11905780
references: Annu Rev Cell Dev Biol. 1997;13:513-609
references: 9442882
references: Biochem Pharmacol. 2007 Jan 1;73(1):56-67
references: 17049494
references: Bull Cancer. 2006 Jul;93(7):677-82
references: 16873076
references: Cancer. 2011 May 15;117(10):2112-9
references: 21523723
references: Oncogene. 2005 May 5;24(20):3236-45
references: 15735720
references: EMBO J. 2011 Aug 12;30(19):3947-61
references: 21841772
references: Apoptosis. 2001 Jun;6(3):191-7
references: 11388668
references: PLoS One. 2012;7(7):e41352
references: 22815994
references: Cancer Metastasis Rev. 2003 Dec;22(4):337-58
references: 12884910
references: Oncogene. 2004 Apr 12;23(16):2950-66
references: 15077156
references: J Med Chem. 2004 Dec 30;47(27):6658-61
references: 15615512
references: Leukemia. 2008 Sep;22(9):1755-66
references: 18596745
references: Mol Cancer Ther. 2009 Nov;8(11):3066-74
references: 19861409
references: N Engl J Med. 2009 Apr 2;360(14):1408-17
references: 19339720
references: Chem Biol. 1998 May;5(5):R97-103
references: 9578633
references: Cancer Treat Rev. 2006 Nov;32(7):504-15
references: 16920269
references: Nat Rev Cancer. 2004 Jun;4(6):470-80
references: 15170449