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

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Abstract

Background

Chemotherapy 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 anti-tumor 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 efficacy of miR-138-5p restoration in combination with PTX to impove BC treatment.

Methods

The 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.

Results

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-G1 and G1 phases of cell cycle by regulating p21, CCND1, and CDK4.

Conclusions

Restored miR-138-5p intensified 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.

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Data Availability

No Data associated in the manuscript.

Abbreviations

BC:

Breast cancer

PTX:

Paclitaxel (Taxol)

FDA:

Food and drug administration

5 FU:

5 fluorouracil

GBM:

Glioblastoma

TMZ:

Temozolomide

PD-L1:

programmed cell death ligand1

NC-miR:

Negative control miRNA

IC50:

half maximal inhibitory concentration

IC25:

quarter maximal inhibitory concentration

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

DMSO:

Dimethyl sulfoxide

MMP2:

matrix metalloproteinase-2

E-cadherin:

epithelial cadherin

AKT:

Protein kinase B (PKB)

p-AKT:

phosphorylated Protein kinase B (PKB)

p-PI3K:

phosphorylated Phosphoinositide 3-kinases

PI3K:

Phosphoinositide 3-kinases

BCL-2:

B-cell lymphoma-2

BAX:

Bcl-2-associated X protein

Caspase 3:

Cysteine-Aspartic Acid Protease 3

Caspase 8:

Cysteine-Aspartic Acid Protease

Caspase 9:

Cysteine-Aspartic Acid Protease 9

P21:

Cyclin-dependent kinase inhibitor 1

CDK4:

Cyclin-dependent kinase 4

CCND1:

cyclin D1

CDK6:

cyclin-dependent kinase 6

OXA:

oxaliplatin

pRb:

retinoblastoma protein

APOBEC3B:

apolipoprotein B mRNA editing catalytic polypeptide-like 3B

TP53INP1:

Tumor protein p53-inducible nuclear protein 1

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Acknowledgements

We thanks Tabriz Immunology Research Center (IRC), Iran for providing facilities to carry out this research.

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Authors and Affiliations

  1. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

    Mina Rasoolnezhad, Reza Safaralizadeh, Mohammad Ali Hosseinpour Feizi & Seyed Mahdi Banan-Khojasteh

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mina Rasoolnezhad, Parisa Lotfinejad & Behzad Baradaran

  3. Social Determinants of Health Research Center, Saveh University of Medical Sciences, Saveh, Iran

    Elmira Roshani Asl

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  1. Mina Rasoolnezhad
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Correspondence to Reza Safaralizadeh.

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Rasoolnezhad, M., Safaralizadeh, R., Hosseinpour Feizi, M. et al. MiR-138-5p improves the chemosensitivity of MDA-MB-231 breast cancer cell line to paclitaxel. Mol Biol Rep 50, 8407–8420 (2023). https://doi.org/10.1007/s11033-023-08711-y

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