Assessment of GSK1904529A as a promising anti-osteosarcoma agent.
Assessment of GSK1904529A as a promising anti-osteosarcoma agent.
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评估GSK1904529A作为有前途的抗骨肉瘤剂。
DOI：
10.18632/oncotarget.17911
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Ji F
中科院分区：
文献类型：
--
作者：
Fei HD;Yuan Q;Mao L;Chen FL;Cui ZH;Tao S;Ji F
胰岛素生长因子-I受体(IGF1R)信号转导是骨肉瘤(OS)细胞增殖的关键机制。GSK1904529A是一种新型的小分子IGF1R激酶抑制剂。检测其对OS细胞的杀伤活性。在已建立的OS细胞系(Saos-2和MG-63)和原代人OS细胞中，GSK1904529A(NM浓度)处理均显著抑制细胞增殖。在分子水平上，GSK1904529A几乎完全阻断了OS细胞中IGF1R的激活，并抑制了AKT-ERK下游的激活。靶向shRNA沉默IGF1R还可抑制AKT-ERK激活和Saos-2细胞增殖。值得注意的是，GSK1904529A不能进一步抑制IGF1R沉默的Saos-2细胞的增殖。在体内，口服GSK1904529A可抑制Saos-2裸鼠移植瘤的生长。综上所述，这些结果表明，GSK1904529A靶向IGF1R在体外和体内都能抑制OS细胞的生长。
The insulin growth factor-I receptor (IGF1R) signaling is a key mechanism for osteosarcoma (OS) cell proliferation. GSK1904529A is a novel small molecule IGF1R kinase inhibitor. Its activity against OS cells was tested. In both established OS cell lines (Saos-2 and MG-63) and primary human OS cells, treatment with GSK1904529A (at nM concentrations) significantly inhibited cell proliferation. At the molecular level, GSK1904529A almost completely blocked IGF1R activation in OS cells, and inhibited downstream AKT-ERK activation. IGF1R silence by targeted shRNA also inhibited AKT-ERK activation and Saos-2 cell proliferation. Significantly, GSK1904529A was unable to further inhibit proliferation of IGF1R-silenced Saos-2 cells. In vivo, GSK1904529A administration orally inhibited Saos-2 tumor growth in nude mice. Together, these results suggest that targeting IGF1R by GSK1904529A inhibits OS cell growth in vitro and in vivo.
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DOI：
10.1016/j.bbrc.2015.02.161
发表时间：
2015-05-01
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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