Research Papers:
Assessment of GSK1904529A as a promising anti-osteosarcoma agent
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Abstract
Hao-Dong Fei1,*, Qi Yuan2,*, Li Mao2, Feng-Li Chen3, Zhao-Hui Cui2, Sha Tao2 and Feng Ji1
1Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
2Department of Endocrinology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
3Clinical Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
*Co-first authors
Correspondence to:
Feng Ji, email: [email protected]
Li Mao, email: [email protected]
Keywords: osteosarcoma, GSK1904529A, IGF1R, proliferation
Received: April 18, 2017 Accepted: May 04, 2017 Published: May 16, 2017
ABSTRACT
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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