Small Interfering RNA Against Tumor and Its Microenvironment Reduced Pancreatic Tumor Growth

Background: Pancreatic cancer is a major oncologic challenge due to its aggressive growth and metastasis. Our previous study showed that adrenomedullin (AM) is highly expressed in pancreatic cancer and stimulates pancreatic cancer cells leading to increased tumor growth and metastasis.1 The current study examines the role of specific AM receptors on tumor and cells resembling the tumor microenvironment (human pancreatic stellate- HPSC, human umbilical vein – HUVEC, and mouse lung endothelial cells- MLEC) and investigates the receptor involved in the autocrine role of AM. Methods: Expression levels of AM and its receptors ADMR and CRLR were assessed by RT-PCR, ELISA, and western blotting. ADMR and CRLR were silenced using siRNA. ADMR-silenced and control cells were used to prepare orthotopic tumors and compared for growth and metastasis in vivo. Angiogenesis was assessed by CD31 staining in vivo and polygon formation in vitro. In vivo studies were conducted using neutral nanoliposomes to systemically deliver human/mouse siRNA to ADMR