Effects of sulfiredoxin silencing on chemosentivity of prostate cancer cells PC3 and DU145

• Grant number: 21/12929-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2021
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Sérgio Luis Felisbino
• Grantee: Micheli Canuto de Lima
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Prostate cancer (CaP) is the second most prevalent cancer in men in Brazil and worldwide. For localized tumors, available treatments have allowed a high rate of cure and survival with the disease. For metastatic tumors, cure rates decrease considerably but can be controlled initially with anti-androgenic therapies. However, most metastatic tumors evolve to their lethal form that is resistant to androgen deprivation, known as metastatic and castration-resistant prostate cancer. For these tumors, treatment with chemotherapy is one of the options, such as with docetaxel, but such treatment has the disadvantages of undesirable side effects and a significant rate of tumor cell resistance. After resistance to docetaxel, the patient's life expectancy significantly decreases, leading to treatment failure. Recent studies suggest that the action of the antioxidant enzyme Sulfiredoxin, overexpressed in more advanced stages of CaP, helps in its chemoresistance, making it more resistant to the oxidative actions of chemotherapy and radiotherapy treatments. Therefore, this study aims to evaluate the chemosensitivity of PC3 and DU145 tumor cells after sulfiredoxin precursor SRXN1 gene silencing, in order to assess its potential to be used as an adjuvant in docetaxel treatment in the clinic. The silencing will be performed through siRNA against the SRXN1 gene, while cell viability and its chemosensitivity will be evaluated by MTT assays. Additional assays that assess the invasive and migratory behavior of these tumor cells (Wound Healing and assays with insert and matrigel) will also be performed. In this study, we hypothesize that SRXN1 silencing makes tumor cells more sensitive to the action of docetaxel.(AU