Antitumor effects of Dasatinib on laryngeal squamous cell carcinoma in vivo and in vitro
- PDF / 873,818 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 78 Downloads / 215 Views
LARYNGOLOGY
Antitumor effects of Dasatinib on laryngeal squamous cell carcinoma in vivo and in vitro Yan Song • Xin Sun • Wei-Liang Bai Wen-Yue Ji
•
Received: 30 November 2012 / Accepted: 29 January 2013 / Published online: 13 February 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com
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
Y. Song X. Sun W.-L. Bai W.-Y. Ji (&) Department of Otolaryngology, Sheng-Jing Hospital, China Medical University, 110004 Shenyang, People Republic China e-mail: [email protected]
application of Dasatinib for the treatment of laryngeal cancer patients Keywords Head and neck cancer Dasatinib Hep-2 cell line Apoptosis
Introduction Laryngeal squamous cell carcinoma is one of the most common squamous cell carcinomas of the head and neck. Laryngeal carcinoma ranks the 11th common kind of cancer in men worldwide, with a tendency toward an increasing occurrence of new cases and deaths annually [1]. More than 95 % of all laryngeal cancers are squamous cell carcinomas. The traditional treatment for squamous cell carcinoma of the larynx was surgery, usually total laryngectomy in advanced cases, followed by radiotherapy. During the last decades, combined modality approaches have been developed, and chemotherapy has been confirmed as a major component of these treatment approaches to enhance loco-regional disease control, reduce distant metastasis, and improve survival in patients with adv
Data Loading...
