International Journal of Women's Health and Reproduction Sciences

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Jul 2020, Vol 8, Issue 3

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Original Article
Reduction in the Viability of Human Cervical Cancer HeLa Cell Line via Indirect Co-culture With Amniotic Fluid-Derived Mesenchymal Stem Cells
Faramarz Rahmatizadeh^1,2,3, Fatima Pashaei-Asl⁴, Manijeh Mohammadi Dehcheshmeh⁵, Sara Rahbar⁶, Maryam LaleAtaei^2,7, Shiva Gholizadeh-Ghaleh Aziz⁸, Jafar Soleimani Rad^{7,93, 7,9,10}
¹Department of Molecular Medicine, Faculty of Advanced Medical Science, Tabriz University of Medical Science, Tabriz, Iran ²Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran ³Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ⁴Molecular Biology Laboratory, Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ⁵School of Animal and Veterinary Sciences, the University of Adelaide, Adelaide, Australia ⁶Department of Reproductive Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran ⁷Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran ⁸Department of Clinical Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran ⁹Department of Reproductive Biology, Faculty of Advanced Medical Science, Tabriz University of Medical Science, Tabriz, Iran ¹⁰Women?s Reproductive Health Research Center, Tabriz University of Medical Sciences Tabriz, Iran
IJWHR 2020; 8: 319-327 DOI: 10.15296/ijwhr.2020.51 Viewed : 2096 times Downloaded : 3658 times. Keywords : Mesenchymal stem cells, HeLa cells, Amniotic fluid, Co-culture, Cell-based therapy
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Abstract

Objectives: This experiment was carried out to evaluate the impacts of unmodified human amniotic fluid-derived mesenchymal stromal/stem cells (hAF-MSCs) on the viability of HeLa cells, as well as the impact of these cells on the expression of common pro-apoptotic and pro-survival genes in tumor cells by establishing an indirect co-culture system. Materials and Methods: To this end, an indirect co-culture system was established, and hAF-MSCs were co-cultured with HeLa cells at a ratio of 1:2 for five days. The cell viability of co-cultured tumor cells was determined after the incubation period. Then, several parameters were examined, including the gene expression of tumor protein 53 (TP53), BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and cyclin-dependent kinase inhibitor 1A (CDKN1A). Finally, gene regulatory networks were analyzed as well. Results: The results of this study confirmed that the co-culture of hAF-MSCs with HeLa cells could decrease the viability of tumor cells. The reduction of HeLa cell viability was accompanied by an increase in BAX, TP53, and CDKN1A while a decrease in BCL-2 gene expression. Eventually, the analysis of the regulatory network revealed that the co-culture of Hela ¬cells with hAF-MSCs activated several transcriptional factors and microRNAs which regulated the expression of these genes. Conclusions: In general, hAF-MSCs exerted the inhibitive effects on the growth of HeLa cells, along with alterations in the expression of common pro-apoptotic and pro-survival genes in a timely and concentration-dependent manner.