Establishment of a cisplatin-resistant oral squamous cell carcinoma cell line: impact on biological behavior

• Grant number: 23/03525-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date until: June 01, 2023
• End date until: May 31, 2024
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Everton Freitas de Morais
• Grantee: Rafaela Fernanda de Souza
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Squamous cell carcinoma (SCC) accounts for more than 90% of all malignant neoplasms of the oral cavity, being considered an aggressive cancer, with an overall 5-year survival of approximately 50%, reduced to less than 30% in advanced stages. In cases diagnosed at an advanced stage, adjuvant chemotherapy treatment is often performed. Cisplatin is a potent chemotherapeutic agent widely used for the oncological treatment of several malignant neoplastic processes, being commonly used in cases of oral SCC. The epithelial-mesenchymal transition (EMT) is known to play an important role in cancer progression and metastasis and has been evaluated as a possible mechanism associated with the chemoresistance induction process. In addition, the modulation of the neoplastic cell phenotype by the EMT process, characterized by the loss of expression of epithelial markers such as E-cadherin and the gain in expression of markers characteristically of mesenchymal cells such as Vimentin, are strongly associated with a worse prognosis in cases diagnosed as OTSCC. However, the development of chemoresistance to cisplatin in the treatment of oral SCC is a frequent challenge in cancer treatment and the mechanisms associated with this process remain unclear. Understanding the process of developing chemoresistance against cancer is a key factor in determining the success of cancer treatment and outlining the appropriate management of cancer patients. The present study aims to establish oral SCC cell lines, evaluating the impact on the biological behavior of SCC-9 cell line when inducing chemoresistance to Cisplatin, analyzing the potential for migration, invasion, proliferation and viability of resistant neoplastic cells, compared to non-resistant neoplastic cells. The objective is also to identify the role of EMT in the induction of chemoresistance, evaluating the expression of E-cadherin and Vimentin markers in the cell lines studied. It is expected, therefore, to obtain better clarifications regarding the biological behavior of chemoresistant oral SCC strains, about understanding the molecular mechanisms acquired in this process.