Analysis of the expression and enzymatic activity of matrix metalloproteinases 2 and 9 in cisplatin-resistant oral cancer cells and effect of Kaempferol on enzymatic inhibition

• Grant number: 24/06135-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2024
• Effective date (End): July 31, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Ricardo Della Coletta
• Grantee: Luma Cavale Christofoleti
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent tumors worldwide, which places it as a major public health problem. Understanding the biological mechanisms and factors that control its aggressive behavior, including situations of acquisition of epithelial-mesenchymal transition (EMT) and chemoresistance to cisplatin, is essential for the development of new and more effective therapies. The aim of this study is to evaluate the expression and activity of matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) in cisplatin-resistant OSCC cells, and to investigate the effect of Kaempferol (KMP), a natural flavonoid existing in several dietary plant sources that has antitumor properties, in the expression and activity of MMP-2 and MMP-9 in parental and cisplatin-resistant OSCC cells. The cisplatin-resistant OSCC cells (SCC9 and HSC3) have already been established and characterized, including their EMT profile. The expression levels of MMP-2 and MMP-9 will be determined by RT-qPCR, whereas the gelatinolytic activity of the enzymes will be assessed by zymography. KMP treatment will be carried out at a concentration of 40 µM, as determined by previous studies. We are anticipating to determine whether the acquisition of cisplatin resistance is associated with the modulation of MMP-2 and MMP-9 expression and activity, and to verify whether KMP is capable of inhibiting these effects, contributing to a better understanding of the aggressive behavior of cisplatin-resistant cells.