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Int J Clin Exp Pathol 2013;6(10):2082-2091

Original Article
Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of
osteoprogenitor cells

Ni-Rong Bao, Meng Lu, Fan-Wen Bin, Zhi-Yong Chang, Jia Meng, Li-Wu Zhou, Ting Guo, Jian-Ning Zhao

Department of Orthopedic Surgery, Jinling Hospital Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Equal

Received August 1, 2013; Accepted August 25, 2013; Epub September 15, 2013; Published October 1, 2013

Abstract: Cancer treatment-related bone loss has become growing problematic, especially in breast and prostate cancer treated with
hormone/endocrine therapy, chemotherapy and radiotherapy. However, bone loss caused by targeted therapy in cancer patients is largely
unknown yet. In present study, a kinase inhibitors screen was applied for MC3T3-E1, a murine osteoprogenitor cell line, and seven kinase
inhibitors (GSK1838705A, PF-04691502, Dasatinib, Masitinib, GDC-0941, XL880 and Everolimus) were found to suppress the cell viability with
dose- and time-dependent manner. The most interesting is that many kinase inhibitors (such as lapatinib, erlotinib and sunitinib) can promote
MC3T3-E1 cell proliferation at 0.01 μM. 4 out of 7 inhibitors were selected to perform the functional study and found that they lead to cell cycle
dysregulation, treatments of PF-04691502 (AKT inhibitor), Dasatinib (Src inhibitor) and Everolimus (mTOR inhibitor) lead to G1 arrest of MC3T3-
E1 cells via downregulation of cyclin D1 and p-AKT, whereas XL880 (MET and VEGFR inhibitor) treatment results in increase of sub-G1 and
G2/M phase by upregulation of p53 protein. Our work provides important indications for the comprehensive care of cancer patients treated with
some targeted drugs. (IJCEP1308001).

Keywords: Cancer treatment-related bone loss, kinases inhibitors screening, osteoprogenitor cells

Address correspondence to: Dr. Jian-Ning Zhao, Department of Orthopedic Surgery, Jinling Hospital Affiliated to School of Medicine, Nanjing
University, 305 Zhongshan East Road, Nanjing 210002, China. Tel: +86-25-80860015; E-mail: zhaojn_jinling@yeah.net