Therapeutic effects of tyroservatide on metastasis of lung cancer and its mechanism affecting integrin–focal adhesion kinase signal transduction

Abstract

Tyroservatide (YSV) can inhibit the growth and metastasis of mouse lung cancer significantly. This study investigated the therapeutic effects of tripeptide YSV on metastasis of human lung cancer cells and explored its possible mechanism that affects integrin–focal adhesion kinase (FAK) signal transduction in tumor cells. YSV significantly inhibited the adhesion and the invasion of highly metastatic human lung cancer cell lines 95D, A549, and NCI-H1299. In addition, YSV significantly inhibited phosphorylation of FAK Tyr397 and FAK Tyr576/577 in the 95D, A549, and NCI-H1299 human lung cancer cells in vitro. And the mRNA level and protein expression of FAK in these human lung cancer cells decreased at the same time. YSV also significantly inhibited mRNA and protein levels of integrin β1 and integrin β3 in the 95D, A549, and NCI-H1299 human lung cancer cells. Our research showed that YSV inhibited adhesion and invasion of human lung cancer cells and exhibited therapeutic effects on metastasis of lung cancer.

Keywords:

• tyroservatide
• integrin
• focal adhesion kinase
• FAK
• MMP-2
• MMP-9

Acknowledgments

This work was supported by grants from the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (grant number: 2014ZX09101005004), National Basic Research Program (973 Program, People’s Republic of China; grant number: 2009CB918903), Natural Science Foundation of Tianjin (grant number: 09JCZDJC19700), PhD Programs Foundation of Ministry of Education of China (grant number: 20101202110001), and Cooperation Project in Industry, Education and Research of Guangdong Province (grant number: 2009B090300430).

Disclosure

The authors report no conflicts of interest in this work.