The p70S6K Specific Inhibitor PF-4708671 Impedes Non-Small Cell Lung Cancer Growth
Background:
p70S6K, a serine/threonine protein kinase, plays a critical role in tumor progression. Overexpression of p70S6K and its activated form, phosphorylated p70S6K (p-p70S6K), has been observed in various cancers and identified as an independent prognostic marker in non-small cell lung cancer (NSCLC). This study investigates the therapeutic potential of PF-4708671, a selective p70S6K inhibitor, in NSCLC.
Methods:
Three NSCLC cell lines—A549, SK-MES-1, and NCI-H460—were treated with PF-4708671 at concentrations of 0.1 μM, 0.3 μM, 1 μM, 3 μM, and 10 μM. Protein expression levels were evaluated via Western blotting. The effects of PF-4708671 on cell proliferation, apoptosis, cell cycle progression, and invasion were assessed in vitro. In vivo tumor growth inhibition was examined using a nude mouse xenograft model.
Results:
PF-4708671 significantly downregulated p-p70S6K and its downstream effector S6, while increasing levels of pro-apoptotic proteins such as BAD, Caspase-3, and ERK. The compound markedly inhibited proliferation and invasion across all three NSCLC cell lines and induced G0–G1 phase cell cycle arrest. However, only modest effects on apoptosis were observed. In vivo, PF-4708671 significantly suppressed tumor growth in nude mice.
Conclusion:
PF-4708671 exhibits potent anti-tumor activity against NSCLC both in vitro and in vivo, primarily by targeting the p70S6K signaling pathway. These findings support p70S6K as a promising therapeutic target and PF-4708671 as a potential candidate for targeted cancer therapy.