Abstract 5276: Enhancement of cisplatin activity against triple negative breast cancer cells by atorvastatin

Abstract

Abstract Breast cancer (BC) is the second most common kind of cancer in the world and the most common among women. Its frequency rate is becoming alarming, being this way a major challenge to global health. It is worth mentioning that the lack of effective therapeutic options, in particular for certain subtypes, such as triple-negative tumor, still present a challenge for clinicians who often have to resort to highly unspecific cytotoxic therapies. Unfortunately, most patients relapse after a period of remission and eventually tumors becomes refractory to frontline therapy. This makes it desirable to identify drugs which synergize with chemotherapeutics and potentially reduce the dose of them that is necessary to treat patients. In the current financial and economical context, drug repositioning is gaining increasing interest as an alternative strategy for drug development. Cancer cells frequently exhibit specific alterations in their metabolic activity. Thus, targeting lipid metabolism in cancer cells could have therapeutic benefits and it does appear as promising auxiliary strategies in the fight against cancer. The present work aimed to investigate the effect of atorvastatin (ATV) on paclitaxel (PTX), cisplatin (CDDP) and olaparib (OLAP) cytotoxic on human BC cell lines MDA-MB-231 and MCF-7, and the mechanisms by which this interaction occurs. ATV decreased cellular metabolic viability (CMV; MTT assay) in a dose-time-dependent manner, especially in MDA-MB-231 being the maximum effect observed in with ATV 100µM (- 90%; p<0.001). In addition, ATV 5µM potentiates PTX and CDDP activities in MDA-MB-231, but not in MCF-7. Moreover, ATV had synergistic inhibitory effects with OLAP decreasing cellular metabolic viability in MDA-MB-231 (- 90%; p<0.001). . Cell cycle distribution analyzed by flow cytometry indicated that coadministration of ATV and CDDP in MDAM-MB-231 result in cell cycle arrest at G0/G1 phase as compared with that of the control and individual drug-treated cells. Altogether, our data suggest that association of ATV with conventional antineoplastic drugs seems to be beneficial, especially when associated with CISP for the MDA-MB-231 lineage. In any event, our study opens a new avenue in the fight against BC while possibly introducing a low cost substance in the portfolio of anticancer drugs and offering a promising strategy to increase the efficacy of them in breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Diandra Zipinotti dos Santos, Isabella dos Santos Guimarães, Nayara Gusmão Tessarollo, Taciane Barbosa Henriques Barbosa Henriques, Paulo Cilas Lyra Junior, Marcele L L. de Souza, Maria C. Gomes, Ian Victor Silva, Leticia B. A. Rangel. Enhancement of cisplatin activity against triple negative breast cancer cells by atorvastatin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5276.