Name: ANA MARIA RODRIGUES DA SILVA
Type: MSc dissertation
Publication date: 08/10/2018
Advisor:
Name |
Role |
|---|---|
| LETICIA BATISTA AZEVEDO RANGEL | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| LETICIA BATISTA AZEVEDO RANGEL | Advisor * |
| PAULO CILAS MORAIS LYRA JUNIOR | External Examiner * |
Summary: High-grade serous ovarian cancer (HGS-OC) is the most frequent cause of deaths among gynecological malignancies. Due to their asymptomatic development as well as the lack of sensitive and specific screening methods, the disease is diagnosed in advanced and incurable stages. Although tumors usually respond to first line taxanes and platinum-based chemotherapy, most patients develop relapse and chemoresistance. Inflammation has been involved in the initiation and development of many types of cancer, including HGS-OC. Recently, the protein components of the innate immune system, known as inflammassome, have been associated with the mechanisms of progression and metastasis of neoplasias, however, its role in drug-resistance is little explored. In this study, through RT-PCR and western blot analysis we investigated the clinical significance of inflammassomas in modulating the chemoresistant phenotype in cisplatin-resistant cells (ACRP) obtained from the parental line of HGS-OC (A2780). Our results have shown that, even though mRNA expression levels of NLRP3 remained unaltered in the ACRP, the NLRP3 protein expression appears to vary in a dose-dependent way with cisplatin treatment, although it does not configure the main event in chemoresistance. An increase in mRNA expression levels of the NLRP1, but not of NLRC4, in resistant cell line ACRP was also obtained. In conclusion, our study was the first to show the involvement of NLRP1 inflammassome in the development and regulation of cisplatin-resistance in HGS-OC cells, making it an attractive target with great therapeutic potential against the disease.
Key words: Ephitelial ovarian cancer, inflammasomes, chemoresistence, cisplatin.
