Details

Autor(en) / Beteiligte

• Wang, Luqi
• Wang, Yue
• Chen, Andy
• Jalali, Aydin
• Liu, Shengzhi
• Guo, Yunxia
• Na, Sungsoo
• Nakshatri, Harikrishna
• Li, Bai-Yan
• Yokota, Hiroki

Titel

Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling

Ist Teil von

• International journal of oncology, 2018-09, Vol.53 (3), p.1001-1012

Ort / Verlag

Athens: Spandidos Publications

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Chemotherapy for suppressing tumor growth and metastasis tends to induce various effects on other organs. Using AZD7762, an inhibitor of checkpoint kinase (Chk) 1 and 2, the present study examined its effect on mammary tumor cells in addition to bone cells (osteoclasts, osteoblasts and osteocytes), using monolayer cell cultures and three-dimensional (3D) cell spheroids. The results revealed that AZD7762 blocked the proliferation of 4T1.2 mammary tumor cells and suppressed the development of RAW264.7 pre-osteoclast cells by downregulating nuclear factor of activated T cells cytoplasmic 1. AZD7762 also promoted the mineralization of MC3T3 osteoblast-like cells and 3D bioprinted bone constructs of MLO-A5 osteocyte spheroids. While a Chk1 inhibitor, PD407824, suppressed the proliferation of tumor cells and the differentiation of pre-osteoclasts, its effect on gene expression in osteoblasts was markedly different compared with AZD7762. Western blotting indicated that the stimulating effect of AZD7762 on osteoblast development was associated with the inhibition of Chk2 and the downregulation of cellular tumor antigen p53. The results of the present study indicated that in addition to acting as a tumor suppressor, AZD7762 may prevent bone loss by inhibiting osteoclastogenesis and stimulating osteoblast mineralization. Key words: checkpoint kinase inhibitor, mammary tumor, osteoclasts, osteoblasts