BIO Türkiye Uluslararası Biyoteknoloji Kongresi, İstanbul, Türkiye, 28 - 30 Eylül 2023, (Yayınlanmadı)
Collagenases (MMP-1, MMP-8, and MMP-13) are members of the matrix metalloproteinase family and are capable of cleaving collagenous extracellular matrix, facilitating tumor invasion and metastasis by creating spaces large enough for cell movement in the dense matrix. In addition, overexpression of collagenases is associated with various diseases such as periodontitis, atherosclerosis, asthma, autoimmune disorders, and corneal epithelial defects. Therefore, identification of MMP inhibitors has emerged as new drug approaches. In this study, we aimed to investigate the effects of MMP-1 inhibitor (piroxicam) and MMP-8 inhibitor I on collagenolytic activity in 8505C thyroid cancer cells by using cell in situcollagen zymography method. The effects of piroxicam and MMP-8 inhibitor I on 8505C thyroid cancer cell viability were detected with crystal violet assay. Sandwich model containing dye-quenched collagen type I (DQ-collagen type I) was generated in 96-well plate. Approximately 1x104 cells were seeded into the wells and then treated with piroxicam and MMP-8 inhibitor I. After the 48-hour incubation, collagenolytic activity was evaluated under the fluorescent microscope. The effects of the inhibitors on MMP-1 and MMP-8 protein expression levels were also analyzed with immunocytochemistry. 100μM piroxicam and 10μM MMP-8 inhibitor I significantly reduced the collagenase activity in 8505C cells by 20.5% (p<0.05) and 36.4% (p<0.05), respectively. However, 100μM piroxicam and 10μM MMP-8 inhibitor I showed no significant effect on MMP-1 and MMP-8 protein expression levels. Piroxicam and MMP-8 inhibitor I effectively reduce collagenolytic activity by binding to active forms of MMP-1 and MMP-8, respectively. Therefore, these inhibitors may have potency to be used as anti-invasive agents in the prevention of thyroid cancer metastasis.