Abstract 3897: MNX1-AS1 expression is positively correlates with expression of drug efflux pumps in ovarian cancer
Authors: Mena Kurt Buchegger , Alvarez Tamara Viscarra , Garrido Daniela León , Pezoa Ramón Silva , Gangas Carmen Ili , Barreto Sindy Cabarca , Flores Marcela Berrios , Zenteno Jorge Sapunar , Mieville Priscilla Brebi 
Published: April 2023

Introduction: Ovarian cancer is one of the most lethal diseases in the female population worldwide. Indeed, the survival rate of ovarian cancer is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main chemotherapy treatment regimens is the use of platinum drugs, specifically carboplatin (CBDCA). Nevertheless, one of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways and tumor suppressors. In the last decade, lncRNAs have been identified as a new element responsible in the regulation of chemoresistant phenotype since they have been linked to multiple biological processes and acting in combination with other mechanism involved in chemoresistant. However, little is known about their role in carboplatin resistance in OC. This study seeks to characterize the effect of lncRNA expression on the chemoresistant phenotype and its correlation with the hyperactivation of drug efflux pumps.

Materials and Methods: Ovarian cancer cell lines A2780-R-CBDCA, A2780-P, UCI-101, OVCAR3 and SKOV3 were used in this study. Chemosensitivity to carboplatin was measured by MTT Assay in 96-well plates after 24, 48 and 72h treatment for determinating IC50 values. Relative expression of MNX1-AS1 associated with CBDCA-resistant phenotype and efflux pumps were evaluated by qRT-PCR.

Results: It was observed that A2780-R-CBDCA, SKOV3 and OVCAR3 cell lines presented the highest resistance indices in contrast to UCI-101 and A2780-P, which turned out to be highly sensitive to treatment with CBDCA. The relative expression of MNX1-AS1 was found elevated in those lines that presented higher levels of resistance to the drug, while in those more sensitive to treatment, the expression of MNX1-AS1 was found to be decreased. On the other hand, the expression levels of the ABCB1 and ABCC1 efflux pumps showed contradictory results in relation to their expression compared to the resistance index shown in each cell line. Mainly, it could be observed that ABCB1 presented a decreased expression in A2780-R-CBDCA, while ABCC1 was found to be increased in the same line.

Conclusion: Our results indicate that the expression of MNX1-AS1 could contribute to the development or maintenance of a chemoresistant phenotype to platinum drugs. Meanwhile, the effect of the expression of MNX1-AS1 on the efflux pumps is not yet possible to relate as a modulator of its hyperactivation. However, their potential participation in this mechanism is not ruled out and new analyzes are necessary to rule out this possible relationship.

Citation Format: Kurt Buchegger Mena, Tamara Viscarra Alvarez, Daniela León Garrido, Ramón Silva Pezoa, Carmen Ili Gangas, Sindy Cabarca Barreto, Marcela Berrios Flores, Jorge Sapunar Zenteno, Priscilla Brebi Mieville. MNX1-AS1 expression is positively correlates with expression of drug efflux pumps in ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3897.