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Article

Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib

  • Authors:
    • Pu Xia
    • Wen-Feng Gou
    • Shuang Zhao
    • Hua-Chuan Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, School of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 139-148
    |
    Published online on: April 24, 2013
       https://doi.org/10.3892/or.2013.2424
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Abstract

Lung cancer accounts for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008. Crizotinib (PF-02341066) is identified as an ATP competitive small-molecular inhibitor for anaplastic lymphoma kinase (ALK). The US Food and Drug Administration (FDA) approved crizotinib to be used for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC in 2011. In the present study, the side population (SP) and main population (MP) cells were obtained from Lewis lung carcinoma cells (LLC) and analyzed by DNA dye (Hoechst 33342) and flow cytometry. LLC SP and MP cells were confirmed as no ALK fusion gene by fluorescence in situ hybridization. The effects of crizotinib on LLC SP and MP cells both in vivo and in vitro were identified. Our results indicate that crizotinib can induce apoptosis and G1 phase arrest in LLC MP cells. Crizotinib used in combination with verapamil can inhibit proliferation of LLC SP cells. Moreover, crizotinib decreased tumor size and weight and inhibited angiogenesis in established xenografted tumors. To analyze the signaling pathway involved, computer simulation, Affymetrix microarray analysis and western blot analysis were performed. In these assays, crizotinib was found to dock into Smad3 and activate the Smad signaling pathway. Overall, these studies demonstrate the antitumor activity of crizotinib in LLC cell line, and provide a novel use for crizotinib.
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Copy and paste a formatted citation
Spandidos Publications style
Xia P, Gou W, Zhao S and Zheng H: Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib. Oncol Rep 30: 139-148, 2013.
APA
Xia, P., Gou, W., Zhao, S., & Zheng, H. (2013). Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib. Oncology Reports, 30, 139-148. https://doi.org/10.3892/or.2013.2424
MLA
Xia, P., Gou, W., Zhao, S., Zheng, H."Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib". Oncology Reports 30.1 (2013): 139-148.
Chicago
Xia, P., Gou, W., Zhao, S., Zheng, H."Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib". Oncology Reports 30, no. 1 (2013): 139-148. https://doi.org/10.3892/or.2013.2424
Copy and paste a formatted citation
x
Spandidos Publications style
Xia P, Gou W, Zhao S and Zheng H: Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib. Oncol Rep 30: 139-148, 2013.
APA
Xia, P., Gou, W., Zhao, S., & Zheng, H. (2013). Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib. Oncology Reports, 30, 139-148. https://doi.org/10.3892/or.2013.2424
MLA
Xia, P., Gou, W., Zhao, S., Zheng, H."Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib". Oncology Reports 30.1 (2013): 139-148.
Chicago
Xia, P., Gou, W., Zhao, S., Zheng, H."Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib". Oncology Reports 30, no. 1 (2013): 139-148. https://doi.org/10.3892/or.2013.2424
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