Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling.
Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling.
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DOI：
10.3892/ijo.2018.4481
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发表时间：
2018-09
影响因子：
5.2
通讯作者：
Yokota H
中科院分区：
文献类型：
--
作者：
Wang L;Wang Y;Chen A;Jalali A;Liu S;Guo Y;Na S;Nakshatri H;Li BY;Yokota H
用于抑制肿瘤生长和转移的化学疗法倾向于引起对其他器官的各种影响。本研究使用AZD 7762（检查点激酶（Chk）1和2的抑制剂），使用单层细胞培养物和三维（3D）细胞球体，检测其对乳腺肿瘤细胞以及骨细胞（破骨细胞、成骨细胞和骨细胞）的影响。结果显示，AZD 7762通过下调活化T细胞胞质1的核因子，抑制4 T1. 2乳腺肿瘤细胞的增殖，并抑制RAW 264. 7前破骨细胞的发育。AZD 7762还促进了MC 3 T3成骨细胞样细胞和MLO-A5骨细胞球体的3D生物打印骨结构的矿化。虽然Chk 1抑制剂PD 407824抑制了肿瘤细胞的增殖和前破骨细胞的分化，但与AZD 7762相比，其对成骨细胞基因表达的影响明显不同。Western blotting结果显示，AZD 7762对成骨细胞发育的促进作用与抑制Chk 2和下调细胞肿瘤抗原p53有关。本研究的结果表明，除了作为肿瘤抑制剂，AZD 7762可以通过抑制破骨细胞生成和刺激成骨细胞矿化来防止骨丢失。
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 bio-printed 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.
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影响因子：
3
作者：
Sausville, Edward;LoRusso, Patricia;Carducci, Michael;Carter, Judith;Quinn, Mary F.;Malburg, Lisa;Azad, Nilofer;Cosgrove, David;Knight, Richard;Barker, Peter;Zabludoff, Sonya;Agbo, Felix;Oakes, Patricia;Senderowicz, Adrian
通讯作者：
Senderowicz, Adrian
使用结构引导的药物设计的新型体内活性CHK1抑制剂的鉴定。
影响因子：
--
作者：
Massey AJ;Stokes S;Browne H;Foloppe N;Fiumana A;Scrace S;Fallowfield M;Bedford S;Webb P;Baker L;Christie M;Drysdale MJ;Wood M
通讯作者：
Wood M
DOI：
10.1093/jnci/53.3.661
发表时间：
1974-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
CAILLEAU, R;YOUNG, R;REEVES, WJ
通讯作者：
REEVES, WJ
影响因子：
9
作者：
通讯作者：
--
影响因子：
6.2
作者：
Kato, Y;Boskey, K;Bonewald, LF
通讯作者：
Bonewald, LF