Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells.

Related Articles

Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells.

Oncol Rep. 2018 Dec;40(6):3223-3234

Authors: Zhao H, Yang Q, Hu Y, Zhang J

Abstract
Triple‑negative breast cancer (TNBC) refers to a heterogeneous group of tumors, for which there is currently a lack of targeted therapies. Poly(ADP‑ribose) polymerase (PARP) inhibitors, phosphatidylinositol 3‑kinase (PI3K) inhibitors and carboplatin (CBP) have demonstrated sufficient efficacy and safety for their use as individual drugs for the treatment of TNBC; however, their effects on TNBC when used as a combination have not been investigated. The primary objectives of the present study were to determine the effects of a combination of CBP, olaparib and NVP‑BKM120 (BKM120), and to investigate the mechanism underlying their effects on TNBC cells. The drug combination was cytotoxic to TNBC cells, both with regards to short‑term and long‑term sensitivity, as determined using colony forming assays, and they exerted strong synergistic effects on MDA‑MB‑231 and CAL51 cell lines. All drugs affected cell cycle progression, and western blotting and immunofluorescence indicated that the the drug combination exerted its cytotoxicity via DNA damage, enhancing non‑homologous end joining repair and inhibiting homologous recombination repair. These data provide a strong rationale to explore the therapeutic use of olaparib in combination with CBP and BKM120 in animal models, and later in clinical trials on patients with TNBC.

PMID: 30272286 [PubMed - indexed for MEDLINE]

https://ift.tt/2RksDaU