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Study On The Effects Of Lycorine On Growth And Metastasis Of Breast Cancer Cells

Posted on:2020-11-22Degree:MasterType:Thesis
Country:ChinaCandidate:P WangFull Text:PDF
GTID:2404330575498010Subject:Biology
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Currently,breast cancer is the most common cancer among women in the world Breast cancer is prone to metastasis,resulting in high recurrence and mortality.At present,the clinical treatment of breast cancer is still based on traditional treatment methods,such as surgery,chemotherapy and radiotherapy.The traditional treatment methods have a large effect,which seriously affect the quality of life of patients.Therefore,searching for new drugs with small side effects and good anti-cancer effect has become the focus of current research.Lycorine which isolated from Amaryllidaceae belongs to isoquinoline alkaloid and has various pharmacological activities and anti-tumor effects.Natural small molecule comounds have attracted more and more attention because of their simple molecular structure and less toxicity.The purpose of this study is to investigate the effects of lycorine on growth and metastasis of breast cancer cells,and further study its mechanism.The main contents of this study are as follows:1.Lycorine inhibited the growth and proliferation of breast cancer cells.MTT assay was used to compare the effects of lycorine and dihydrolysine on the activities of breast cancer cells.It was found that lycorine inhibited the activity of breast cancer better.2.Lycorine affected the expression of proteins in breast cancer MDA-MB-231 cells.MDA-MB-231 cells were found to have differential proteins after treatment with lycorine through TMT quantitative proteomics technology.The analysis of these differential proteins revealed that lycorine could affect Wnt signaling pathway.3.Lycorine inhibited the breast cancer cells growth,induced cells apoptosis and regulated cell cycle.At the cellular level,the results of crystal violet staining and colony forming ability experiments indicated that lycorine inhibited the growth and proliferation of breast cancer cells.And lycorine could change the mitochondrial membrane potential of breast cancer cells by JC-1 probe.Hoechst 33342 staining showed that the number of apoptotic corpuscles increased with increased concentration of lycorine in the field of view.Flow cytometry and Western blotting indicated lycorine could induce apoptosis of MDA-MB-231 and MCF-7 cells,and the higher concentration of lycorine,the more obvious the apoptosis.Lycorine could affect the cycle distribution in breast cancer cells,and arrested it in G2/M phase.4.Lycorine inhibited the migration of breast cancer cells in a time-and concentration-dependent manner.The results of WB showed that the expressions of?-catenin,N-cadherin and F-actin were decreased,and the expression of GSK-3? and E-cadherin were increased5.4T1-Luc cells were inoculated into BALB/c mice to establish a tumor-bearing mouse model.In vivo results showed that lycorine suppressed the growth and metastasis of breast tumors.In summary,lycorine inhibited the growth and metastasis of breast cancer cells in vivo and in vitro,arrested the cell cycle in the G2/M phase and induced cell apoptosis.In addition,lycorine inhibited EMT process in breast cancer cells by regulating the expression of key proteins in Wnt classical signaling pathway.The study provided a certain experimental basis for the study of lycorine and its anti-tumor mechanism.Meanwhile,it also provided a new research direction for the clinical treatment of breast cancer.
Keywords/Search Tags:Lycorine, Breast cancer, Wnt/?-catenin signaling pathway, EMT, Proliferation and metastasis
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