Open Access

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

  • Authors:
    • Hui Zhao
    • Qianxi Yang
    • Yunhui Hu
    • Jin Zhang
  • View Affiliations

  • Published online on: September 20, 2018     https://doi.org/10.3892/or.2018.6716
  • Pages: 3223-3234
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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December-2018
Volume 40 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhao H, Yang Q, Hu Y and Zhang J: Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells. Oncol Rep 40: 3223-3234, 2018
APA
Zhao, H., Yang, Q., Hu, Y., & Zhang, J. (2018). Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells. Oncology Reports, 40, 3223-3234. https://doi.org/10.3892/or.2018.6716
MLA
Zhao, H., Yang, Q., Hu, Y., Zhang, J."Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells". Oncology Reports 40.6 (2018): 3223-3234.
Chicago
Zhao, H., Yang, Q., Hu, Y., Zhang, J."Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells". Oncology Reports 40, no. 6 (2018): 3223-3234. https://doi.org/10.3892/or.2018.6716