The p70S6K Specific Inhibitor PF-4708671 Impedes Non-Small Cell Lung Cancer Growth

PloS One
Zhixin QiuWeimin Li

Abstract

As a serine/threonine protein kinase, p70S6K plays an important role in tumor cells. Evidence has revealed overexpression of p70S6K and phosphorylated p70S6K (p-p70S6K) in various tumor tissues, with these proteins identified as independent prognostic markers in non-small cell lung cancer (NSCLC). In this study, we explored the role of the p70S6K specific inhibitor PF-4708671 in NSCLC. Three NSCLC cell lines (A549, SK-MES-1, and NCI-H460) were treated with PF-4708671 at five different concentrations, including 0.1μM, 0.3μM, 1μM, 3μM and 10μM, and protein levels were determined by Western-blot. Then, PF-4708671's effects were assessed both in vitro (cell proliferation, apoptosis, cell cycle distribution, and invasion) and in vivo. The expression levels of p-p70S6K and the downstream effector S6 were significantly reduced by PF-4708671. Diametrically opposite, the downstream protein levels of BAD, Caspase3 and ERK had increased after treatment with PF-4708671. In addition, PF-4708671 drastically inhibited cell proliferation and invasion ability in A549, SK-MES-1 and NCI-H460 cells in vitro, causing cell cycle arrest in G0-G1 phase. Limited effects of PF-4708671 were observed on apoptosis in the three NSCLC cell lines assessed. Im...Continue Reading

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Citations

Jun 24, 2016·Pharmaceutical Patent Analyst·Hermann Am Mucke
Mar 10, 2017·International Journal of Radiation Biology·Ye WangZhenyu Lin
May 29, 2018·Oncotarget·Fernando M SimabucoRodrigo E Tamura
Sep 22, 2019·Journal of Cellular and Molecular Medicine·Zhixin QiuWeimin Li
Sep 26, 2020·Therapeutic Advances in Medical Oncology·Zachary D CreesNeelu Puri
Aug 11, 2018·Molecular Cancer Therapeutics·Nellie K McDanielDeric L Wheeler

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Methods Mentioned

BETA
Protein Assay
electrophoresis
xenograft
flow cytometry
xenografts

Software Mentioned

Quantity One 1 - D Analysis
SPSS

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