1. Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-beta
- Author
-
Michiyuki Hakozaki, Junji Suzumiya, Yuichi Yamashita, Hiroshi Iwasaki, Jun Ohishi, Tamotsu Takeuchi, Mikiko Aoki, Kazuki Nabeshima, and Akira Ogose
- Subjects
Cancer Research ,Receptor, Platelet-Derived Growth Factor alpha ,medicine.medical_treatment ,Gene Expression ,Mice, SCID ,Nerve Sheath Neoplasms ,Piperazines ,Receptor, Platelet-Derived Growth Factor beta ,Mice ,In vivo ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Cell Line, Tumor ,medicine ,Genetics ,Animals ,Humans ,RNA, Messenger ,Phosphorylation ,Cell Proliferation ,biology ,Cell growth ,Growth factor ,Imatinib mesylate ,Pyrimidines ,Oncology ,Cell culture ,Gene Knockdown Techniques ,Benzamides ,Mutation ,biology.protein ,Cancer research ,Imatinib Mesylate ,Neoplastic Stem Cells ,Female ,Stem cell ,Platelet-derived growth factor receptor ,Nerve sheath neoplasm ,Research Article - Abstract
Background Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed. Methods The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model. Results The results showed expression of platelet-derived growth factor receptor-β and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 − 4.6 μM) in three of six cell lines. Knockdown of PDGFR-β by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis. Conclusions The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.
- Published
- 2013