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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

PF-04449913 Inhibits Proliferation and Metastasis of Colorectal Cancer Cells by Down-regulating MMP9 Expression through the ERK/p65 Pathway

Author(s): Yejiao Ruan, Guangrong Lu, Yaojun Yu, Yue Luo, Hao Wu, Yating Shen, Zejun Gao, Yao Shen, Zhenzhai Cai* and Liyi Li*

Volume 17, 2024

Published on: 13 October, 2023

Article ID: e150923221164 Pages: 13

DOI: 10.2174/1874467217666230915125622

open_access

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Abstract

Introduction: Colorectal cancer remains a life-threatening malignancy with increasing morbidity and mortality worldwide. Therefore, new and effective anticolorectal cancer therapeutics are urgently needed.

Methods: In this study, we have studied the anti-tumor properties and potential mechanisms of PF-04449913. Colorectal cancer cell viability was reduced by PF-04449913 in a dose-dependent manner. The migration and invasion ability of malignant colon cells were attenuated by the drug, as demonstrated by the Transwell test. Moreover, PF-04449913 repressed the phosphorylation levels of ERK and other proteins, and the expression levels of MMP9. The anti-tumor effects of the drug in vivo were demonstrated in BALB/c-nude mice models, and PF-04449913 inhibited the malignant phenotype of colorectal cancer cells, including reduction of tumor size and promotion of apoptosis. At the molecular level, PF-04449913 induced a significant decrease in ERK and p65 protein phosphorylation levels and inhibited MMP9 protein expression.

Results: Both in vivo and in vitro results showed PF-04449913 to demonstrate antitumor effects, which have been proposed to be mediated through blockade of the ERK/p65 signaling pathway, and subsequent repression of MMP9 expression.

Conclusion: Our study provides a new perspective on the potential clinical application of PF-04449913 in the treatment of colorectal cancer.

Keywords: PF-04449913, Proliferation, Metastasis, Colorectal cancer, MMP9 expression, ERK/p65 pathway.

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