Impact of SERPINH1 (serpin family H member 1) knockdown on oral squamous cell carcinoma cells response to cisplatin

Abstract

The Oral Squamous Cell Carcinoma (OSCC), the main subtype of cancer in the oral cavity, is characterized by a poor prognosis, resulting from a very aggressive local growth and high rates of locoregional recurrence. The treatment of choice for OCCs is surgery, with radiotherapy and/or chemotherapy being applied as adjuvants. Cisplatin is the most used chemotherapeutic drug for the treatment of OSCCs, though it is well-known that it can have an incomplete effect and induce chemoresistance. The mechanisms related to these unwanted effects are complex, heterogeneous, and partially known. One of these mechanisms is the adaptive cellular response based on heat shock proteins (HSP) overexpression, which is capable of neutralizing the cytotoxic effects of platinum-based drugs. SERPINH1 (serpin family H member 1), also known as HSP47, was initially known for its importance for the synthesis and secretion of collagen, but nowadays its participation in many of the events associated with tumorigenesis is well-established, including modulation of response to chemotherapy. As the results of our recently completed project (FAPESP process number 2018/16077-6) demonstrated that SERPINH1 is overexpressed in OSCCs and its high levels are associated with poor outcomes, the aim of this project is to assess the impact of SERPINH1 neutralization in the cytotoxic response promoted by cisplatin. Two OSCC cell lines (HSC3 and SCC9), which had their high levels of SERPINH1 neutralized by the transduction of lentiviral particles expressing specific shRNAs, will be treated with increasing concentrations of cisplatin and evaluated regarding viability (cytotoxicity), distribution in the cell cycle phases and apoptotic rates. These cells will also be cultured in a 3D spheroid model and tested for their sensitivity to cisplatin. It is expected with this project to determine the influence of SERPINH1 on OSCC response to cisplatin, contributing to a better biological understanding of the role of SERPINH1 overexpression in OSCCs.(AU)