TY - JOUR T1 - Epigenetic Regulation of APAF-1 Through DNA Methylation in Pancreatic Cancer JF - Anticancer Research JO - Anticancer Res SP - 3765 LP - 3779 DO - 10.21873/anticanres.14366 VL - 40 IS - 7 AU - AUSRA LUKOSIUTE-URBONIENE AU - AUGUSTINA MAZEIKE AU - MINTAUTE KAZOKAITE AU - GIEDRE SILKUNIENE AU - MANTAS SILKUNAS AU - VIDMANTAS BARAUSKAS AU - GIEDRIUS BARAUSKAS AU - ANTANAS GULBINAS AU - ALBERTAS DAUKSA AU - ZILVINAS DAMBRAUSKAS Y1 - 2020/07/01 UR - http://ar.iiarjournals.org/content/40/7/3765.abstract N2 - Background/Aim: Apoptotic peptidase activating factor 1 (APAF-1) is essential regulator of apoptosis and inactivation by DNA methylation is common event in numerous cancer types. We investigated the regulation of APAF-1 through DNA methylation in pancreatic cancer. Materials and Methods: Datasets from 44 patients after pancreatoduodenectomy and the pancreatic adenocarcinoma (PDAC) cell lines Capan-2 and MIA PaCa-2 treated with decitabine were analyzed by RT-PCR, immunoblotting, methylation-specific PCR analysis, apoptosis and viability assays to identify effects of APAF-1 regulation. Results: APAF-1 mRNA and protein levels were significantly down-regulated, and APAF-1 methylation status was associated with perineural invasion in PDAC. Decitabine inhibited cell viability and increased apoptosis rates, however failed to restore APAF-1 mRNA and protein levels in cells. Conclusion: APAF-1 gene hypermethylation may contribute to the progression of PDAC through perineural invasion. Decitabine could sensitize pancreatic cancer cells to apoptosis and growth retardation, however, not directly through the APAF-1 demethylation process. ER -