Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells in vitro

Yin,Lin‑Lin; Wen,Xin‑Mian; Lai,Qing‑Hua; Li,Jing; Wang,Xiu‑Wen

doi:10.3892/ol.2018.8120

Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells in vitro

Authors:
- Lin‑Lin Yin
- Xin‑Mian Wen
- Qing‑Hua Lai
- Jing Li
- Xiu‑Wen Wang
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Affiliations: Department of Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Clinical Laboratory, The Fourth Hospital of Jinan, Jinan, Shandong 250031, P.R. China, Department of Oncology, The Central Hospital of Jinan, Jinan, Shandong 250013, P.R. China, Department of Hematology and Oncology, The Fourth Hospital of Jinan, Jinan, Shandong 250031, P.R. China
Published online on: February 27, 2018 https://doi.org/10.3892/ol.2018.8120
Pages: 6469-6474

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Abstract

Lenalidomide is an immunomodulatory drug and possesses anti-angiogenic and immunomodulatory activities against multiple myeloma. The present study assessed the in vitro effect of lenalidomide combined with cisplatin on MDA‑MB‑231, a triple‑negative breast cancer (TNBC) cell line and explored the underlying molecular mechanism of this combination. Cell viability, apoptosis and the protein expression of phosphorylated (p) and total extracellular signal‑regulated kinase (ERK), B‑cell lymphoma-2 (Bcl-2), caspase‑3, cleaved poly‑adenosine diphosphate‑ribose polymerase (cPARP), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured in MDA‑MB‑231 cells treated with different concentrations of lenalidomide, cisplatin and their combination using different biochemical assays. Lenalidomide demonstrated no significant effect on the cell viability of MDA‑MB‑231 cells, even at high concentrations, whereas lenalidomide in combination with cisplatin, significantly reduced cisplatin IC50 from 7.8 to 3.0 µM in MDA‑MB‑231 cells. In addition, lenalidomide and cisplatin in combination significantly induced cell apoptosis by 1.6- and 1.38-fold, respectively compared with lenalidomide and cisplatin alone (P<0.05). The expression levels of VEGF, bFGF and Bcl-2 proteins were significantly reduced (P<0.01), whereas caspase‑3 and cleaved PARP expression were significantly increased in MDA‑MB‑231 cells treated with the combination compared to those treated with single agents (P<0.01). Lenalidomide treatment alone significantly reduced the p-ERK level compared with the control (P<0.05) and cisplatin treatment alone significantly increased it (P<0.01), however treatment with them in combination significantly reduced the p-ERK level in MDA‑MB‑231 cells compared with cisplatin treatment alone (P<0.05). In conclusion, the present study provides the basis for using lenalidomide in combination with cisplatin in TNBC therapy.

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