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Study On The Anti-lung Cancer Effect Of The Monomelic Compound Of The Traditional Chinese Medicine Goose Grass And The Traditional Chinese Medicine Swine Tooth Soap

Posted on:2021-03-30Degree:MasterType:Thesis
Country:ChinaCandidate:Q HuFull Text:PDF
GTID:2434330632455745Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Cancer has been one of the highest mortality diseases in the world,and the incidence and mortality of lung cancer have the first place in the world.The prevention and treatment of lung cancer should be placed as a priority.Nowadays,various chemotherapy,radiotherapy,targeted and immune therapies are used in cancer.They can prolong a bit survival time of patients,but the quality of patients' life is not improved.Recently,some chinese medicines have a good effect on treating certain cancers,so they are studyed by more and more people.My present study can be divided into following two parts:one part is the anti-lung cancer activity of 32 compounds isolated from medicinal herb Centipeda minima and the other is the effect of medicine herb Gleditsiae fructus abnormalis on lung cancer.These researches are the foundation for the clinical application and anti-lung cancer research of medicinal herb Centipeda minima.1.The anti-lung cancer activity of 32 compounds isolated from medicinal herb Centipeda minimaObjective:We previously showed that a component of the medicinal herb Centipeda minima,6-O-angeloylplenolin(6-OAP),exhibits strong anti-lung cancer activity in vitro and in vivo.In this study,the effects of 32 compounds from Centipeda minima were tested to identify those with anti-lung activity and explore their anti-lung cancer mechanism.Methods:The effects of small molecules on cell proliferation of H460,A549,H1975,H1299,and H520 cells were tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide(MTT)assays,and the IC50 values were calculated.The compounds with better activity were selected.The apoptotic cells were analyzed by Annexin V-propidium iodide(PI)method.And the changes in the protein,which is associated with apoptosis,cell proliferation and autophagy were evaluated by Western Blot.Simultaneously,we tested the effect of this compound on PD-L1Results:Among the 32 compounds,10(31.3%)ones were able to suppress cell proliferation by 15%or more.Three compounds,CM-19(Arnidiol),6-OAP(CM-25),and CM-26(Helenalin-isovalerate),showed significant inhibitory effect on the five lines with relatively low IC50 values.And CM-26 has a best activity than others.Flow cytometry analysis showed that CM-26 could significantly induce lung cancer cell apoptosis(P<0.01),and Western Blot results showed that CM-26 induced apoptosis of H1975 and H1299 cells with cleavage of PARP and activation of Caspase-3 and Caspase-8.CM-26 can activate the expression of autophagy marker protein LLC and inhibit the expression of p-AKT and p-ERK in a concentration-dependent manner,And CM-26 increased the expression of PD-L1 in lung cancer cells.Conclusion:Centipeda minima bears several components that show significant inhibitory effects on lung cancer cells.CM-26 can significantly inhibit lung cancer cell proliferation and induce apoptosis and autophagy.The mechanism of anti-lung cancer may be related to the inhibition of p-AKT and p-ERK.CM-26 can not decrease the expression of PD-L1.2.The effect of medicine herb Gleditsiae fructus abnormalis on lung cancerObjective:To study the anti-lung cancer activity of Gleditsiae fructus abnormalis in vivo and in vitro.Methods:The effects of Gleditsiae fructus abnormalis on cell proliferation of H460,A549 and H1299 cells were tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide(MTT)assay,and the IC50 values were calculated.The apoptotic cells were analyzed by Annexin V-propidium iodide(PI)method,and the cell cycle was analyzed by PI method.The changes in the protein,which is associated with apoptosis,cell cycle,were evaluated by Western Blot.C57/BL mice were numbered,injected with LLC cells(1×106)via tail vein,two days after xenograft,the mice were randomized into groups,and were treated with vehicle control(ddH2O)or Gleditsiae fructus abnormalis at 20,40 mg/kg/day,for 21 day.After 38 days of injection,the mice were executed and dissected.We took images,weighed lungs and performed statistical analysis to explore the anti-tumor activity in vivo.Results:Gleditsiae fructus abnormalis showed significant inhibitory effect on the three lines with relatively low IC50 values.And H1299 cells are more sensitive than others to this drug.Flow cytometry analysis showed that Gleditsiae fructus abnormalis could significantly induce lung cancer cell apoptosis at 50 ?g/mL for 48 h(P<0.01).And Western Blot results showed that the drug induced apoptosis with cleavage of PARP in H1299 cells.Flow cytometry analysis showed that Gleditsiae fructus abnormalis can significantly block the cell cycle of H1299 cells in G2/M phase(P<0.01),and the Western Blot results showed that it can inhibit the expression of Cyclin D1 in a concentration-dependent manner.In vivo,compared with the control group,the mice in the low and high dose groups had significantly lowered tumor weight(P<0.01),and had a significant anti-tumor effect.Conclusion:Gleditsiae fructus abnormalis showed significant inhibitory effects on lung cancer cells.It can significantly inhibit lung cancer cell proliferation by inducing apoptosis and blocking the cell cycle.It has an anti-tumor activity in mice.
Keywords/Search Tags:centipeda minima, lung cancer, apoptosis, gleditsiae fructus abnormalis, inhibition of cell proliferation
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