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

Abstract

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. 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. 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,.