Project description:Paeoniflorin (PF) is an active monoterpene glycoside extracted from Paeonia lactiflora Pall. Recent studies showed that PF has anti-tumor effects in various types of cancer. However, the function of PF in pancreatic cancer (PA) is largely unexplored. Here, we showed that PF suppressed growth of PA cell lines Capan-1 and MIAPaCa-2, and profoundly sensitized these cells to X-ray irradiation. Through a microarray analysis, we identified tumor-suppressor candidate gene HTRA3 as the most increased gene upon PF treatment in Capan-1 cells. Ectopic expression of HTRA3 led to reduced cell growth and increased expression of apoptotic protein Bax, suggesting a tumor suppressive role of HTRA3 in PA cells. Together, our results provide a set of genetic and biologic proofs that PF inhibited PA cell growth by upregulation of HTRA3.
Project description:Pancreatic cancer cells are inherently highly resistant to spontaneous or chemotherapy-induced apoptosis. The human pancreatic tumor cell line Capan-1 (pRB+/p16-) was stably transfected with p16 expression constructs or control plasmids to functionally inactivate pRB. Three independent experiments were conducted
Project description:We profile gene expression with or without SIRT4 overexpression in pancreatic cancer cell line CAPAN-2 to find the different genes and pathways regulated by SIRT4.
Project description:Based on data-independent acquisition (DIA)-mass spectrometry (MS), we assessed the epithelial/mesenchymal phenotype of three pancreatic cancer cell lines: CAPAN-1, PANC-1 and MIA PaCa-2 in 2D cell culture.
Project description:Expression analysis of human pancreatic cancer cell lines (Capan-1, Panc-1, Panc-1+ve and Panc-1-ve) and pancreatic ductal cell line (HPDE)
Project description:Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis. To explore the underlying molecular mechanisms, we used a model based on primary ASC derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells. Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix (ECM) gene expression in ASC. We investigated the function of two markers of the fibroblastic transition highly induced by cancer cells: a long non-coding RNA LINC01614 and a Wnt signaling modulator SFRP4. By using ASC with either SFRP4 or LINC01614 knocked out (ko), we showed that both genes are required for Wnt / TGFβ signaling and ECM induction in ASCs by Capan1. Analysis of changes in Capan-1 genes that rely on LINC01614 and SFRP4 expression in ASC also identified the Wnt and TGF pathways. SFRP4 ko in ASCs suppressed both migration and invasion of Capan-1 cells. We show that tumors in SFRP4 ko mice have less desmoplasia, less epithelial dedifferentiation, reduced growth rate, and reduced progression to metastasis. We conclude that SFRP4 promotes cancer progression in pancreatic cancer and is a promising therapeutic target.
