Simvastatin Possesses Antitumor and Differentiation‐Promoting Properties that Affect Stromal Cells in Giant Cell Tumor of Bone
Publication in refereed journal

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其它資訊
摘要Giant cell tumor of bone (GCTB) is a locally aggressive destructive bone lesion. The management of pulmonary metastasis and local recurrence after the surgical treatment of GCTB remains a challenge. Pathologically, stromal cells in GCTB are known as primary neoplastic cells and are recognized as incompletely differentiated preosteoblasts. Therefore, inducing GCTB stromal cells to differentiate into cells with a mature osteoblastic phenotype may stop tumor growth and recurrence. In this study, we aimed to investigate how simvastatin, a clinically approved and commonly used statin that has been known to promote the maturation of cells of the osteogenic lineage, affects GCTB stromal cells. We found that simvastatin effectively inhibited cell viability by suppressing proliferation and by inducing apoptosis in GCTB stromal cells. Moreover, simvastatin treatment upregulated the expression of genes related to osteogenic maturation, such as runt‐related transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN), and increased the mineralization of the extracellular matrix in GCTB stromal cells. Ingenuity Pathway Analysis was used to discover that the vitamin D receptor pathway was involved in the simvastatin‐induced osteogenic differentiation of GCTB stromal cells by upregulating the 1,25‐dihydroxyvitamin D metabolism. Taken together, this in vitro study demonstrates the antitumor and differentiation‐promoting effects of simvastatin on GCTB stromal cells and suggests the possibility of using simvastatin as an adjuvant therapy for GCTB. These findings support further clinical investigation of the efficacy of using simvastatin as an adjuvant therapy for GCTB to reduce recurrence and distant metastasis after surgical treatment.
出版社接受日期31.08.2019
著者Carol PY Lau, Cathy SH Fung, Kwok Chuen Wong, Yu‐Hsuan Wang, Lin Huang, Stephen KW Tsui, Oscar K Lee, Shekhar Madhukar Kumta
期刊名稱Journal of Orthopaedic Research
出版年份2020
月份2
卷號38
期次2
出版社Wiley
出版地US
頁次297 - 310
國際標準期刊號0736-0266
電子國際標準期刊號1554-527X
語言美式英語
關鍵詞Cancer / Tumors, Therapeutics

上次更新時間 2020-05-08 於 00:47