en عمومى General پژوهشي Research <div><strong>Background: </strong>Mammalian cell division is regulated by a complex includes cyclin-dependent kinases (Cdks) and cyclins, Cdk/cyclin complex. The activity of the complex is regulated by Cdk inhibitors (CKIs) compressing CDK4 (INK4) and CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family. Hypermethylation of CKIs has been reported in various cancers. DNA methyltransferase inhibitors (DNMTIs), such as decitabine and 5-aza-2&prime;-deoxycytidine (5-aza-CdR) can reactivate hypermethylated genes. The current study aimed to evaluate the effect of 5-aza-CdR on the expression of p16INK4a, p14ARF, p15INK4b genes, cell viability, and apoptosis in HCC PLC/PRF5 and pancreatic cancer MIA Paca-2 cell lines.<br> <strong>Materials and Methods: </strong>In this laboratory trial, both cell lines were treated with 5-aza-CdR (0, 1, 2.5, 5, 10, 15, and 20 &mu;M) to determine cell viability and then with 3 &mu;M to obtain cell apoptosis and relative gene expression. The cell viability, apoptosis, and genes expression were investigated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay, flow cytometry, and Real-Time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), respectively.<br> <strong>Results: </strong>5-aza-CdR indicated significant inhibitory effect with all used concentrations (P = 0.003). The apoptotic effect of 5-aza-CdR on PLC/PRF5 cells in comparison to pancreatic cancer MIA Paca-2 cells was more significant (P= 0.001). Real-time quantitative PCR analysis revealed that treatment with 5-aza-CdR (3 &mu;M) for 24 and 48h up-regulated p16INK4a, p14ARF, p15INK4b genes expression significantly(P=0.040).<br> <strong>Conclusion: </strong>Reactivation of p16INK4a, p14ARF, p15INK4b genes by 5-aza-CdR can induce apoptosis and inhibit cell viability in HCC, PLC/PRF5, and pancreatic cancer, MIA Paca-2, cell lines.</div> Apoptosis, 5-aza-2'-deoxycytidine-5'-monophosphate, Gene expression, Viability 219 228 http://ijpho.ssu.ac.ir/browse.php?a_code=A-10-550-6&slc_lang=en&sid=1 Masumeh Sanaei No Research center for non-communicable diseases, Jahrom University of medical sciences, Jahrom, Iran Fraidoon Kavoosi 0000- 0001- 7761- 7912 No Research center for non-communicable diseases, Jahrom University of medical sciences, Jahrom, Iran Maedeh Mohammadi Yes Student of Research Committee, Jahrom University of medical sciences, Jahrom, Iran Maryam Khanezad No Department of anatomy, school of medicine, Tehran University of medical science, Tehran, Iran.