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

Abstract

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 IC 50 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.

Liposomal Taro Lectin Nanocapsules Control Human Glioblastoma and Mammary Adenocarcinoma Cell Proliferation

“…On the other hand, breast adenocarcinoma cells displayed a less favorable panorama when compared to literature results. Liposomal tarin nanocapsules inhibited breast cancer cell proliferation, displaying an IC 50 of 71.38 μg/mL, while doxorubicin and cisplatin exhibited IC 50 of 0.50 and 2.30 μg/mL, respectively [39,40] (Table 2). It should be considered that conventional chemotherapeutic drugs are highly cytotoxic to healthy cells since their effective dose against tumoral cells is usually close to the cytotoxic doses for healthy cells, meaning they display a low selective index, the ratio between the CC 50 (the concentration required to cause 50% cytotoxicity) and IC 50 (the concentration required to cause 50% inhibition).…”

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

“…KJ-Pyr-9 was applied in the concentrations of 1, 5, 10, and 20 µM, and DMSO was used as control. Lenalidomide was used in concentrations of 30, 100, and 300 µM, and DMSO was applied as solvent control [ 35 , 36 ]. For the co-treatment, 10 ng/mL TNF-α, 100 µM PDTC [ 37 , 38 ], and 300 µM Dexa [ 39 , 40 ] were applied in the following conditions: (1) TNF-α, (2) TNF-α + Dexa, (3) TNF-α + PDTC, (4) TNF-α + Dexa + PDTC, (5) Dexa, (6) PDTC, (7) Dexa + PDTC.…”

Lenalidomide Enhances CAR-T Cell Activity Against Solid Tumor Cells

“…For example, when lenalidomide was combined with cisplatin to target triple-negative breast cancer cell line MDA-MB-231, lenalidomide reduced the half-maximal inhibitory concentration (IC 50 ) value of cisplatin. Compared with single drugs, their combined application significantly inhibits angiogenesis and induces apoptosis 46 . In another study, lenalidomide and 1,25-D3 (1α, 25-dihydroxyvitamin D3, the biologically active form of vitamins D) were also targeted to MDA-MB-231 tumor cells (with vitamin D resistance).…”