The role of palbociclib on the alterations in CDKN2, CCNE1, E2F3, MDM2 expressions as target genes of miR-141

• Published in: PloS one Vol. 19; no. 8; p. e0306545
• Main Authors: Baziyar, Mohammad Ali, Hosseini, Arshad, Jandel, Farinush
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.08.2024; Public Library of Science (PLoS)
• Subjects: Analysis; Antimitotic agents; Antineoplastic agents; Biology and Life Sciences; Blood proteins; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Care and treatment; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; Cyclin E - genetics; Cyclin E - metabolism; Cyclins; Data management; E2f3 gene; Estrogen; Estrogen receptors; Estrogens; Ethylenediaminetetraacetic acid; FDA approval; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genes; Health aspects; Humans; MCF-7 Cells; MDM2 protein; Medical prognosis; Medicine and Health Sciences; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Phosphorylation; Piperazines - pharmacology; Proteins; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Pyridines - pharmacology; Real time; Regulatory proteins; Retinoblastoma; RNA; Software; Tumor cell lines; Variance analysis; Iran
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0306545

According to WHO, Breast cancer is widely considered to be the first or second cause of cancer-related death almost universally. Cell cycle disruption, either in the form of uncontrolled expression of cyclins or because of the suspension in negative regulatory proteins (CDK inhibitors), was found to cause breast cancer. Palbociclib as specific CDK4/6 inhibitor is used for the treatment of ER+ metastatic cancers. In this study, we are looking to investigate the effect of palbociclib on breast cancer cells and evaluate the changes in the expression of some genes involved in the cell cycle as target genes of miR-141 after treatment with this drug. We used MCF7 as functional estrogen and non-invasive and MDA-MB-231 cell lines as triple-negative type of breast cancer and a model for more aggressive. MCF7 and MDA-MB-231 cell lines were cultured in DMEM medium. After counting cells and measuring viability, Palbociclib was administered at varying doses using the IC50 obtained from MTT, with the treatment given at two time points of 24 and 72 hours. RNA was extracted from untreated and treated cells and RNAs were converted to cDNA in the end. Gene expression changes were investigated by real-time PCR. Data management and analysis were conducted using GraphPad Prism 5.01 software. Among investigated genes, E2F3 gene was not significantly affected by Palbociclib in any of cell lines and time points. Besides, the expression of CCNE1 gene was significantly suppressed. It seems this drug was unable to reduce the expression of MDM2 gene significantly in triple negative (MDA-MB-231) cancer cells; however, a decrease was observed in luminal A (MCF-7) cells. CDKN2A and miR-141 genes expression increased significantly after treatment which can be aligned with palbociclib in proliferation inhibition.