MiR-138-5p improves the chemosensitivity of MDA-MB-231 breast cancer cell line to paclitaxel

Abstract

BackgroundChemotherapy is a predominant strategy for breast cancer (BC) treatment and paclitaxel (PTX) has been known as a conventional chemotherapeutic drug. However, insensitivity of BC cells to PTX limits the antitumor effects of this agent. MicroRNAs are closely related to BC which are suggested as therapeutic factors in the combination therapy of BC. We examined the possible e cacy of miR-138-5p restoration in combination with PTX to impove BC treatment. Methods and ResultsThe human breast cancer cell line MDA-MB-231 was transfected with miR-138-5p mimics and treated with PTX, in a combined or separate manner. The MTT assay was accomplished to determine inhibitory doses of PTX. Annexin V/PI assay and DAPI staining were applied to evaluate apoptosis. Flow cytometry was applied to determine cells arrested in different phases of the cell-cycle. Expression levels of molecular factors involved in cell migration, proliferation, apoptosis, and cell cycle were determined via western blotting and qRT-PCR.MiR-138-5p combined with PTX suppressed cell migration via modulating MMP2, E-cadherin, and vimentin and sustained colony formation and proliferation by downregulation of the PI3K/AKT pathway.qRT-PCR showed that miR-138-5p increases BC chemosensitivity to PTX by regulating the apoptosis factors, including Bcl-2, Bax, Caspase 3, and Caspase 9. Moreover, miR-138-5p restoration and paclitaxel therapy combined arrest the cells in the sub-G 1 and G 1 phases of cell cycle by regulating p21, CCND1, and CDK4. ConclusionsRestored miR-138-5p intensi ed the chemosensitivity of MDA-MB-231 cell line to PTX, and the combination of miR-138-5p with PTX might represent a novel approach in BC treatment.

Propofol overcome Tamoxifen resistance in breast cancer by modulating tumorogenesis, immune response and metabolism

“…Indeed, the misregulation in cell cycle related siganling pathways results in the unlimited proliferation of tumour cells. Moreover, it was reported that one of the approaches for increasing the sensitivity of cancer cells to chemotherapeutics was to in synergy them with cell cycle regulators [24]. Preclinical studies have shown that Propofol can significantly inhibit the development of breast cancer tumors[29; 31; 36].…”