Expression of Forkhead box M1 in soft tissue leiomyosarcoma: Clinicopathologic and in vitro study using a newly established cell line

Akira Maekawa, Kenichi Kohashi, Nokitaka Setsu, Masaaki Kuda, Kunio Iura, Takeaki Ishii, Tomoya Matsunobu, Tetsuya Nakatsura, Yukihide Iwamoto, Yoshinao Oda

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

Leiomyosarcoma (LMS) of soft tissue is a sarcoma with smooth-muscle differentiation, and conventional chemotherapy does not improve its outcome. The application of novel antitumor agents and precise prognostication has been demanded. The expression of the protein Forkhead box M1 (FOXM1), a member of the FOX family, is considered an independent predictor of poor survival in many cancers and sarcomas. However, the expression status of FOXM1 in LMS is poorly understood. The purposes of this study were to examine the correlation between the expression of FOXM1 and clinicopathologic or prognostic factors and to clarify the efficacy of FOXM1 target therapy in LMS. We evaluated the immunohistochemical expressions of FOXM1 using 123 LMS tumor specimens. Univariate and multivariate survival analyses revealed that FOXM1 expression was associated with poor prognosis in LMS. An in vitro study was then carried out to examine the antitumor effect of a FOXM1 inhibitor (thiostrepton) and siRNA on a novel LMS cell line, TC616. We also assessed the efficacy of the combined use of doxorubicin and thiostrepton. Thiostrepton showed dose-dependent antitumor activity and TC616 cells treated with the combination of thiostrepton and doxorubicin showed lower proliferation compared to those treated with either drug individually. FOXM1 interruption by siRNA decreased cell proliferation and increased chemosensitivity. In conclusion, FOXM1 has potential to be a therapeutic target for LMS.

本文言語英語
ページ(範囲)95-102
ページ数8
ジャーナルCancer Science
107
1
DOI
出版ステータス出版済み - 1 1 2016

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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