Potential using of microRNA-34A in combination with paclitaxel in colorectal cancer cells
Hadis Soltani-Sedeh1, Shiva Irani2, Reza Mirfakhraie3, Masoud Soleimani4
1 Department of Biology, Science and Research Branch, Islamic Azad University; Stem Cell Technology Research Center, Tehran, Iran
2 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-331, Tehran
Department of Biology, Science and Research Branch, Islamic Azad University, P.O. Box: 1477893855, Tehran
Source of Support: None, Conflict of Interest: None
Background: MicroRNAs are small noncoding RNAs which modulate gene expression at different levels. It has been shown that downregulation of miR-34a occurs in varieties of cancers including colorectal cancer (CRC). In this study, we investigated the potential tumor inhibitory effects of miR-34a alone or in combination with paclitaxel in CRC cells.
Materials and Methods: SW480 cells were transduced with lentiviral overexpressed miR-34a. First, using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, the effect of miR-34a induction alone or in combination with paclitaxel on the cell viability and cell proliferation were estimated. Then, the expression level of target genes was measured using quantitative reverse transcription-polymerase chain reaction analysis. Eventually, the role of miR-34a and paclitaxel on cell cycle were determined with flow cytometry.
Results: Gene expression analysis showed that miR-34a downregulates the expression of BCL2 and SIRT1 genes at mRNA level. Furthermore, miR-34a has a potential to reduce cell viability and cell cycle arrest at G1 phase. Combination of paclitaxel with overexpression of miR-34a significantly decreased cell viability compared to cell treated with miR-34a or paclitaxel alone. Interestingly, a combination of miR-34a and paclitaxel arrested cell cycle at two phases.
Conclusion: Our results suggested that combination therapy of miR-34a and paclitaxel could be considered as the potential treatment of CRC.