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Effects And Mechanisms Of Quercetin On Proliferation And Apoptosis Of Human Breast Cancer MCF-7 Cells

Posted on:2022-05-16Degree:MasterType:Thesis
Country:ChinaCandidate:D C JiangFull Text:PDF
GTID:2504306515480594Subject:Pharmacy
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Background: Worldwide,the proportion of breast cancer(BC)in female diseases is gradually increasing.As one of the effective treatments for breast cancer in clinical applications,chemotherapy has limited its therapeutic effect due to its many side effects.Therefore,the focus of the public and medicine has gradually shifted to natural plant ingredients with anti-cancer properties to alleviate cancer problems.Flavonoids such as quercetin have attracted great attention as natural substances and may be used as alternative or complementary drugs in the treatment of breast cancer.As a natural polyphenol compound,quercetin has a wide range of pharmacological activities such as anti-cancer,anti-inflammatory,anti-diabetic,anti-viral and anti-allergic.In recent years,it has been found that quercetin plays an anticancer role by regulating the proliferation,apoptosis and angiogenesis of tumor cells.There are few studies on the inhibition of quercetin on the proliferation and apoptosis of human breast cancer cell line MCF-7,and its detailed anti-cancer mechanism has not been confirmed.Therefore,human breast cancer cell MCF-7 will be used as the research object of this project to explore the therapeutic effect of quercetin on breast cancer,and further explore the relevant potential mechanism of its anticancer effect,so as to add more experimental basis for the optimization of breast cancer treatment.Aim: To investigate the effect of quercetin on the expression of long non-coding RNA GAS5 and its possible mechanism on the proliferation and apoptosis of breast cancer cells.Methods: Breast cancer cells MCF-7 were treated with different concentrations of quercetin.Cell viability was detected by MTT assay,cell proliferation and cloning ability were measured by plate colony formation assay,and cell apoptosis was examined by Annexin V-FITC/PI double staining assay.Meanwhile,MCF-7 cells were treated with different concentrations of quercetin(40,80,160μM),small interfering RNA of GAS5(si GAS5)and quercetin(80μM)in combination with si GAS5,respectively.The expressions of GAS5,Notch1,Jagged1,Hes1,Bcl-2,Bax and Caspase3 in MCF-7 cells were analysed by q RT-PCR and western blot.Results: The appropriate concentrations of quercetin were 40μM,80μM and 160μM.Quercetin treated MCF-7 cells for 24,48,and 72 hours,and it was found that quercetin at concentration of 40 μM significantly inhibited the proliferation of MCF-7 cells,and quercetin at concentration of 80μM or 160μM not only inhibited proliferation but also induced apoptosis.Different concentrations of quercetin(40,80,160μM)could up-regulate the expressions of GAS5,Bax,Caspase3,and down-regulate the expressions of Notch1,Jagged1,Hes1,Bcl-2 in MCF-7 cells.In comparison with sncRNA group,the expressions of GAS5,Bax and Caspase3 were effectively down-regulated and the expressions of Notch1,Jagged1,Hes1 and Bcl-2 were significantly up-regulated after transfection with si GAS5.When MCF-7 cells transfected with si GAS5 and then cotreated with 80μM quercetin,we found that compared to quercetin combined with sncRNA,the expressions of Notch1,Jagged1,Hes1 and Bcl-2 were up-regulated,while GAS5,Bax and Caspase3 were down-regulated.Conclusions: Quercetin promotes the expression of GAS5 in MCF-7 cells,and regulates the Notch1 signaling pathway by targeting GAS5,thereby inhibiting the proliferation and inducing the apoptosis of MCF-7 cells.
Keywords/Search Tags:Quercetin, breast cancer, long non-coding RNA GAS5, Notch1 signaling pathway, apoptosis, targeting
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