4.7 Article

EnDuo, a novel derivative of Endostar, inhibits the migration of colon cancer cells, suppresses matrix metalloproteinase-2/9 expression and impedes AKT/ERK activation

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 134, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.111136

Keywords

Endostatin; Endostar; Colon cancer; Migration; Matrix metalloproteases; PI3K/AKT signaling pathway; MAPK/ERK signaling pathway

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The study demonstrates that EnDuo inhibits the migration of colon cancer cells in a dose-dependent manner by reducing the phosphorylation of AKT and ERK proteins and inhibiting the expression of MMP-2 and MMP-9 proteins. This provides novel insights into the potential clinical applications of EnDuo against colon cancers in the future.
Background/aims: Colon cancer remains a life-threating disease with increasing morbidity and mortality worldwide despite the advancement in modern medical treatment. Therefore, novel and effective anti-colon cancers drugs are urgently needed. In this study, we investigated the anti-metastatic property EnDuo, a modified version of Endostar, and the underlying mechanisms. Methods: Colon cancer cells were treated with different concentrations of EnDuo (50 mu g/mL, 100 mu g/mL, 200 mu g/mL), and Endostar (100 mu g/mL) as positive control. Cell Counting Kit-8 assay was performed to test the effect of EnDuo on cell viability. A scratch wound assay and transwell assay were employed to evaluate the relocation and motility of malignant colon cells following treatment with EnDuo. Western blot analysis was used to determine inhibitory effects of EnDuo by detecting the phosphorylation level of AKT and ERK proteins, and the expression of MMP-2 and MMP-9 proteins. Results: Our results showed that EnDuo impedes the migration of colon cancer cells in a dose-dependent manner. At the molecular level, EnDuo induced a significant reduction in the phosphorylation of AKT and ERK proteins, and inhibited the expression of MMP-2 and MMP-9 proteins. Conclusions: Collectively, these results demonstrate that EnDuo exhibits a comparable anti-metastatic effect by suppressing the migration of colon cancer cells. Possibly, EnDuo interrupts the PI3K/AKT/ERK signaling pathway to arrest cell migration. Our study provides a novel insight to the potential clinical applications of EnDuo against colon cancers in the future.

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