Middle East Journal of Cancer

Paclitaxel May Inhibit Epithelial-Mesenchymal Transition Properties of Triple-negative Breast Cancer Cell Line via Altering the Expression of EMT-promoting and –inhibiting MicroRNAs

Document Type : Original Article(s)

Authors

Navideh Haghnavaz 1, 2, 3
Faezeh Asghari 4
Najibeh Shekari 2
Dariush Shanehbandi 2
Mahsa Javadian 2
Ali Mohammadi 2
Bahzad Baradaran 2
Tohid Kazemi 2

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

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

3 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

4 Infections and Tropical Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran

https://doi.org/10.30476/mejc.2019.78716.0
Abstract
Background: Abnormal expressions of microRNAs are related to various cancers such as breast cancer for which paclitaxel is widely used as a chemotherapeutic agent. We aimed to investigate the effect of paclitaxel treatment on the expression level of miR-199a-5p and miR-10b, involved in epithelial-mesenchymal transition (EMT) process in breast cancer cell lines.
Methods: Human breast cancer cell lines BT-474, SKBR-3, MDA-MB-231, and MCF-7 were cultured and MTT assay was used to determine IC50 of paclitaxel. RNA was extracted, cDNA was synthesized, and the expression level of miRNAs and genes was quantitatively determined using real-time PCR.
Results: After treatment with paclitaxel, the expression level of miR-199a-5p significantly decreased in MCF-7 and SKBR-3 cell lines, while it increased in MDA-MB-231 and BT-474. The expression level of miR-10b was also significantly reduced in MCF-7, MDA-MB-231, and SKBR-3 and increased in BT-474 cell lines following treatment with paclitaxel. Our results further indicated that paclitaxel reduced the expression level of vimentin and MMP-9 in MDA-MB-231 cell line.
Conclusion: Our findings revealed the increased expression of EMT-inhibitor miR-199a-5p and the decreased expression of metastamir miR-10b after treatment of MDA-MB-231 metastatic breast cancer cell line. Reduced expressions of vimentin and MMP-9 were also observed, corroborating the inhibition of metastasis markers in this type of breast cancer. The therapeutic effect of paclitaxel may in part be due to the change in the balance of EMT-promoting and EMT-inhibiting miRNAs.

Keywords

Breast cancer
MiR-199a-5p
MiR-10b
Paclitaxel
Vimentin
MMP-9

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