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Effect Of Nitrosoalkane On Proliferation And Migration Of Human Ovarian Cancer SKOV3 Cells And Its Mechanism

Posted on:2019-05-22Degree:MasterType:Thesis
Country:ChinaCandidate:H WangFull Text:PDF
GTID:2394330548962130Subject:Biochemistry and Molecular Biology
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In recent years,cancer has become the public health issue most concerned by people and has seriously affected human health.Ovarian cancer has been one of the leading causes of death of female gynecological malignancies in the 21 st century.Every year,ovarian cancer causes 662,000 deaths worldwide,and about half of these patients appear in China.In addition,ovarian cancer is hidden due to onset,the tumor is located deep in the pelvic cavity,so most patients with ovarian cancer are difficult to detect in the early stage,it is difficult to accurately identify and judge,until the occurrence of physical symptoms and be diagnosed,has become the stage of cancer,and accompanied by peritoneal cultivation and distant transfer.At present,the treatment methods for ovarian cancer mainly include surgical treatment,chemotherapy,radiation therapy,and biological therapy.However,these treatment methods are not only expensive but cause toxic side effects to the body of the patients.Nitric oxide(NO)is a multifunctional gas molecule produced by tumors,stroma,and endothelial cells,and it exerts multiple mechanisms of action in tumor biology through various pathways.Nitrosoalkane,ovarian cancer,proliferation and apoptosis,cell migration.There is increasing evidence that NO signaling pathways are involved in ovarian cancer growth,apoptosis,tumor stromal cell interactions,angiogenesis,and response to chemotherapy.Alkylation of nitric oxide compounds as a substance involved in the NO signaling pathway to promote the activity of soluble guanylate cyclase in vitro,and can promote the production of downstream cGMP.At present,there is no systematic study of alkylation.Effect of Nitric Oxide Compounds on proliferation and migration of tumor cells.Through this experimental study,the MTT method was used to preliminarily screen out the effects of the three types of RNO compounds on the growth of ovarian cancer cell SKOV-3 and show a tendency to inhibit cell viability,and nitrocyclohexane was used as the nitrocyclohexane.The research subjects investigated showed that nitrocyclohexane not only inhibited the cell viability and proliferation of ovarian cancer cell SKOV-3,but also caused an increase in the cell membrane permeability of SKOV-3 cells,the collapse of nuclei,and induction of cell apoptosis.Inhibition of cell cycle progression in G2/S phase,increased ROS levels,apoptotic changes in mitochondrial membrane potential,detected of apoptosisassociated proteins PARP,cleaved-PARP,Bcl2,cleaved-Caspase-3,cleaved-Caspase-8,cleaved-Caspase-9 by western blot The expression of in cells activates the Caspase cascade.The above shows that nitrocyclohexane can cause apoptosis of ovarian cancer cell SKOV-3 and significantly regulate intracellular oxidative stress.We detected differences in cGMP levels between normal ovarian epithelial cells Hesopic and ovarian cancer epithelial cells SKOV-3,and after treatment with nitrocyclohexane,we found that nitrocyclohexane can reduce cGMP levels to some extent.We detected the expression levels of NO signaling pathway and NOTCH signaling pathway related proteins in ovarian cancer cell SKOV-3 at the protein level,and determined that NOTCH protein was stimulated by nitrocyclohexane through drug treatment.The decrease in expression level and the coordinated regulation of the decrease in the expression of GUCY1B3 protein in the NO signaling pathway regulate the decrease in cellular cGMP content.
Keywords/Search Tags:Nitrosoalkane, ovarian cancer, proliferation, apoptosis, cell migration
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