| Objective: In the development and progression of prostate cancer,signals transmitted by androgen receptor-based signaling pathways play a crucial role,and androgen deprivation therapy(ADT)is the standard for advanced prostate cancer.For treatment,most patients had significant effects after the first contact with ADT.However,although ADT treatment can relieve the progression of prostate cancer in the early stages,most prostate cancers eventually progress from androgen-dependent progression to androgen-independent prostate cancerover time.Resistance,also known as CRPC.Most clinical studies have shown that the risk of cardiovascular and cerebrovascular diseases in patients with prostate cancer receiving ADT is increased,and lipid metabolism is disordered,but the mechanism is not yet clear.In this study,prostate cancer cell lines were processed to simulate the ADT process and CRPC process,and the changes in the levels of sugar-lipid metabolism-related genes before and after treatment were observed.This experiment is a pre-experiment,mainly to provide direction and ideas for investigating the mechanisms of glucose and lipid metabolism disorder after prostate cancer patients receive ADT.Methods: First,we have selected two types of prostate cancer cell lines,the LNCa P cell line and the C4-2 cell line.Based on the LNCa P cell line,a castration-resistant prostate cancer cell model,the CD-LNCa P cell line,was established.MTT assay was used to detect the growth activity of CD-LNCa P.The three cell lines were divided into five groups and treated with the dose of drug(0 nm DHT,1 nm DHT,10 nm DHT,10 nm DHT+casodex,10 nm DHT+MDV3100)respectively.The q PCR assay was used to detect the changes in the levels of genes related to sugar and lipid metabolism in prostate cancer cells in each cell line.Through plasmid transfection technology,knock down the level of AR-V7 gene in CD-LNCa P cells,and then detect and verify whether it is ideal.QPCR was used to detect the changes of genes related to glucose and lipid metabolism in CD-LNCaP cells before and after knockdown.Results: 1.The level of changes in the sugar-lipid metabolism-related genes in each of the above prostate cancer cell line 5 groups before and after treatment was measured by the q PCR method.The results of LNCAP and C4-2 cell lines showed that the gene levels of FASN and HMG COA genes in the normal group were significantly higher than those in the castration group.In addition,in the LNCa P cell line,the gene levels of FASN and HMG COA in the CD-LNCa P group were significantly higher than those in any other group.2.The cell growth and cell viability of CD-LNCa P stable cell lines were significantly higher than that of LNCa P cells by MTT assay.3.The level of changes in the lipid-lipid lipid metabolism-related genes in the above-described AR-V7 knockdown CD-LNCa P prostate cancer cells was examined by q PCR.The results showed that the FASN and HMGCo A genes were knocked down by AR-V7 compared to CD-LNCa P cells.The CD-LNCa P cells were significantly reduced.Conclusions: It can be seen that in androgen-dependent prostate cancer,ADT can significantly reduce the FASN and HMGCo A gene levels,thereby inhibiting the proliferation of prostate cancer cells.However,in castration-resistant prostate cancer cells,FASN and HMGCo A gene levels were significantly higher than those of androgen-dependent prostate cancer,and were insensitive to ADT.Thus,in castration-resistant prostate cancer prostate cancer cells,there are independent androgen receptor signaling pathways that regulate tumor cell lipid metabolism and growth.The expression of AR-V7 is increasing during the progression of castration-resistant prostate cancer cells.We found that the expression levels of FASN and HMGCo A related to lipid metabolism were reduced by reducing the AR-V7 gene level in castration-resistant prostate cancer cells.reduce.This is of great significance for the further study of the mechanism of abnormal lipid metabolism in CRPC patients and will benefit many patients in the future. |
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