Inhibition of angiogenesis and tumor progression of MK-0429, an integrin αvβ₃ antagonist, on oral squamous cell carcinoma.

ABSTRACT:

Purpose

Integrin αvβ₃ is an essential molecule for tumor angiogenesis. This study aimed to investigate the anti-tumor effect of MK-0429, an integrin αvβ₃ antagonist, on oral squamous cell carcinoma (OSCC) through its inhibitory effect on angiogenesis.

Methods

In this study, we investigated the effect of MK-0429 on cellular function and angiogenesis in vitro with the use of an immortalized human umbilical vein endothelial cell, HUEhT-1, which is immortalized by the electroporatic transfection of hTERT. The effect of MK-0429 on the integrin αvβ₃ signaling pathway was examined by FAK, MEK1/2 and ERK 1/2 phosphorylation. The anti-angiogenic effect of MK-0429 was evaluated by in vitro tube formation assay. The anti-tumor effect on OSCC was assessed by administrating MK-0429 to mouse oral cancer xenografts.

Results

MK-0429 inhibited cell proliferation, migration, and adhesion of HUEhT-1 in a dose-dependent manner. FAK, MEK and ERK phosphorylation were significantly blocked by MK-0429 treatment. Tube formation was suppressed by MK-0429 in dose-dependent manner. Tumor progression was significantly suppressed by MK-0429 administration in mouse oral cancer xenografts. Histological study revealed that MK-0429 decreased tumor vascularization.

Conclusion

These results indicated integrin αvβ₃ as a therapeutic target for OSCC and suggested that MK-0429 might be clinically applicable as an anti-tumor agent with potent anti-angiogenic activity.

SUBMITTER: Nakagawa T 

PROVIDER: S-EPMC9587112 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature