Resistance to multikinase inhibitor actions mediated by insulin like growth factor-1

Journal of Experimental & Clinical Cancer Research : CR
Catia LippolisBrian I Carr

Abstract

Blood platelet numbers are correlated with growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) both stimulated HCC cell growth and migration, and antagonized the growth-inhibitory and apoptotic effects of Regorafenib, multikinase growth inhibitor, on HCC cell lines. We evaluated the effects of human insulin-like growth factor-1 (IGF1), a mitogen contained in platelets, on the Regorafenib-mediated growth inhibition. An Elisa kit was used to evaluate hPL IGF1 concentrations. The effects of IGF1 on cell proliferation were assessed with MTT assay and analysis of cell cycle progression. Apoptosis assays, scratch assay and Transwell assay were performed to measure apoptosis, cell migration and invasion respectively. Western blots were performed by standard protocols. IGF1 antagonized growth inhibition exerted by Regorafenib on HCC cell lines. Moreover the mitogen blocked Regorafenib-induced apoptosis and decreased the rate of cell migration and invasion. The IGF1 effects were in turn antagonized by actions of a potent IGF1 receptor inhibitor, GSK1838705A, showing that the IGF1 receptor was involved in the mechanisms of IGF1-mediated blocking of R...Continue Reading

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Citations

May 28, 2016·Journal of Experimental & Clinical Cancer Research : CR·Xiu-Yan HuangXin-Yu Huang
Sep 24, 2016·Oncotarget·Deeksha VishwamitraHesham M Amin
Oct 9, 2015·Journal of Experimental & Clinical Cancer Research : CR·Francesca MegiorniCarlo Dominici
Oct 23, 2015·Journal of Experimental & Clinical Cancer Research : CR·Bojiang ChenWeimin Li
Mar 14, 2020·Cancers·Maria Grazia RefoloRosalba D'Alessandro
Jul 24, 2020·Pharmacological Reports : PR·Tanweer HaiderVandana Soni
Mar 7, 2021·International Journal of Molecular Sciences·Mai-Huong Thi NgoYen-Hua Huang

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Methods Mentioned

BETA
ELISA
Assay

Software Mentioned

Image J
Muse Cell Analyzer
GraphPad Prism

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