Increased Expression of the ABCA1 and ABCA3 Transporter Genes is Associated with Cisplatin Resistance in Breast Cancer Cells

Al-Shumary, Dhiya Salih; Al-Shammari, Ahmed Majeed; Rasheed, Marrab N.

doi:10.31557/APJCP.2023.24.11.3969

Increased Expression of the ABCA1 and ABCA3 Transporter Genes is Associated with Cisplatin Resistance in Breast Cancer Cells

Document Type : Research Articles

Authors

¹ Department of Microbiology, Faculty of Medicine, Kufa University, Najaf, Iraq.

² Department of Experimental Therapy, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq.

³ Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq.

10.31557/APJCP.2023.24.11.3969

Abstract

Objective: Breast cancer (BC) is a highly malignant neoplasm with resistance to therapeutics that are related to genes associated with multidrug resistance. The excessive expression of ATP-binding cassette transporters (ABCs) genes, including ABCA1 and ABCA3, is a primary factor contributing to the increased effluent of cell-toxic drugs and subsequent treatment resistance. Therefore, the current work aimed to explore the role of ABCA1 and ABCA3 in chemoresistance activity against cisplatin in breast cancer cells. Methods: The current study compared the AMJ13 breast cancer cells derived from a woman Iraqi patient, which are hormone receptor-negative, with MCF-7 breast cancer cells, which are hormone receptor-positive. Cytotoxic assay (CCK-8 assay) is used to measure the cell’s viability and cytotoxic activity after it has been treated with cisplatin. Morphological Study using crystal violet stain to examine cytological changes was conducted. Quantitative RT-PCR is used to measure how much the ABCA1, and 3 genes mRNA are being expressed before and after treatment. Results: The CCK-8 assay found that IC50 values of cisplatin in AMJ13 and MCF-7 cells were 202.2 µg/ml and 90.23 µg/ml, respectively. The IC50 value of AMJ13 is 2-fold higher than in MCF-7 cells. The QPCR study revealed that breast cancer cell lines AMJ13 and MCF-7 subjected to cisplatin showed upregulated levels of ABCA1 and ABCA3 expression. Experiments with cytotoxicity assays demonstrate that higher expression of ABCA1 and ABCA3 in AMJ13 and MCF-7 breast cancer cell lines is linked to their resistance. Conclusion: The findings of this study suggest that the ABCA1 and ABCA3 transporters play a significant role in the resistance to cisplatin and,

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