title: Isoquercitrin inhibits the progression of pancreatic cancer in vivo and in vitro by regulating opioid receptors and the mitogen-activated protein kinase signalling pathway.
abstract: Pancreatic cancer is a common malignant tumour that affects individuals worldwide. In recent years, the incidence and mortality rates of pancreatic cancer have continuously increased. Currently, the primary clinical treatment methods for pancreatic cancer include surgical resection, chemotherapy and radiotherapy. However, these treatment methods rarely produce satisfactory therapeutic outcomes. Extensive research has also proven that the effective components of several traditional Chinese medicines, particularly flavonoids extracted from plants, have significant antitumour effects. Isoquercitrin, which is one of the flavonoids found in Bidens pilosa extracts, has a significant antitumour effect. However, the antitumour effect of isoquercitrin and its mechanism of action remain unclear. The objective of the present study was to investigate the effect of isoquercitrin on the progression of pancreatic cancer and to further understand the biological characteristics of the participation of isoquercitrin in the progression of pancreatic cancer. In vitro, we found that a therapeutic dose of isoquercitrin significantly inhibited proliferation, promoted apoptosis and induced cell cycle arrest within the G1 phase in pancreatic cancer cells. Isoquercitrin activated caspase-3, -8 and -9 and reduced the mitochondrial membrane potential. In addition, isoquercitrin inhibited the expression level of the δ opioid receptor; however, isoquercitrin had no effect on the κ and µ opioid receptors. Furthermore, isoquercitrin inhibited extracellular signal-regulated kinase (ERK) phosphorylation and promoted c-Jun N-terminal kinase (JNK) phosphorylation. In vivo, we found that a therapeutic dose of isoquercitrin significantly inhibited xenograft growth in nude mice. In summary, the present study demonstrated that isoquercitrin inhibits human pancreatic cancer progression in vivo and in vitro and that its molecular mechanism may be closely related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery and Medical Oncology, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi 541001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery and Medical Oncology, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi 541001, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000201:enzymology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry; D011957:Receptors, Opioid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011957:Receptors, Opioid; C016527:isoquercitrin; D011794:Quercetin; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases