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Studies On The Mechanism Of Apoptosis Induced By Medicarpin And Griffithavixanthone In Lung Cancer Cells

Posted on:2022-05-07Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y ShenFull Text:PDF
GTID:2491306602960309Subject:Chemical Engineering and Technology
Abstract/Summary:
Lung cancer is the most common primary malignant tumor in the lung.Lung cancer is one of the most morbid and mortality types in the world,and the annual morbidity and mortality rates are increasing.In our country,about 816,000 new cases and 715,000 deaths of lung cancer in 2020,it is the highest number of new cases and deaths among all types of cancer.Traditional treatment methods,such as surgical treatment,radiotherapy and chemotherapy,can inhibit tumor growth and prevent cancer metastasis,but the treatments are not selectivity,not only it kills tumor cells but normal cells are also damaged,so patients often suffer from diarrhea,hepatic dysfunction,low-immunity and other adverse reactions.In addition,patients are susceptible to drug resistance after treatments,leading to a recurrence or metastasis.Emerging treatment methods,such as targeted therapy and immunotherapy,get more attention because of better therapeutic effect.Patients with the treatments,suppress the progress of lung cancer,extend the survival time,and combining with other treatment methods can achieve synergistic killing of lung cancer cells.However,targeted and immunotherapy treatments are expensive and also face some problems such as susceptibility to drug resistance,it is necessary to develop new specific therapeutic methods.Previous research demonstrated that some natural compounds extracted from natural herbs have anti-tumor activity.For example,artemisinin and its derivatives dihydroartemisinin and artesunate isolated from the Artemisia annua exhibit antitumor activity.As chemosensitising effects,they combining with platinum anticancer drugs are used in breast,lung,pancreas cancer in vivo.Two natural compounds,medicarpin and Griffipavixanthone,were selected by screening,but the therapeutic effects and mechanisms of them are not clear.Medicarpin extracted from alfalfa plant exhibited anti-tumor activity in A549 and H157 cell lines from experiments in whose IC50 values are 206.8 μM and 102.7μM,respectively.Besides,medicarpin induced 53.52%A549 and 50.18%H157 cell lines apoptosis,and arrested cell cycle at the G2 phase in A549 cells.It was found that the growth of mouse tumor was significantly inhibited with the treatment of medicarpin through the mouse tumor models,the inhibition rate is 60.3%,the survival time was significantly extended,and medicarpin could also play a better anti-tumor function in the body.Further study of molecular mechanisms has found that medicarpin is involved in the regulation of apoptosis pathways by promoting the expression of apoptosis genes and proteins such as Bax and Bakl to induce apoptosis in cells,while reducing the expression of BID proteins to inhibit cell proliferation and reduce cell growth.Another natural compound Griffipavixanthone derived from Garcinia exhibits anti-tumor activity.Compared with medicarpin,Griffipavixanthone exhibited stronger inhibition in lung cancer cells,the IC50 values are 12.5 μM and 9.4μM in A549 and H157 cells respectively.36.10%A549 and 42.70%H157 cell lines induced apoptosis with the treatment of Griffipavixanthone,73.70%A549 cells were induced cell cycle arrest at the G2 phase.In summary,two natural compounds,medicarpin and Griffithavixanthone,have anti-lung cancer activity in vitro,which inhibit cell proliferation and promote apoptosis.It was shown that medicarpin inhibited tumor cell growth and prolonged survival time through the mouse tumor models.The study of molecular mechanisms has found that medicarpin was involved in the regulation of cell proliferation and apoptosis pathways to achieve the removal of lung cancer cells by promoting apoptosis and inhibiting cell proliferation.
Keywords/Search Tags:lung cancer, therapy, natural compound, medicarpin, Griffipavixanthone
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