Establishment Of Abiraterone-resistant Cell Line Of Human Prostate Cancer PC-3 Cells And Drug Resistance Test

[Backgroup and propose]:Prostate cancer is a common malignant tumor of-the male genitourinary system,and its incidence has ranked first among male malignant tumors in European and American countries.In China,the incidence of prostate cancer is not as good as that of European and American countries,but its incidence and detection rate are also rising in recent years.Endocrine therapy is one of the important treatments for prostate cancer.Traditional endocrine drugs will gradually develop drug resistance after a period of administration,and hormone-dependent prostate cancer gradually turns into castration-resistant prostate cancer.As a newly developed endocrine drug,abiraterone acetate has been used as a first-line treatment for patients with castration-resistant prostate cancer.Its main principle is to inhibit the synthesis of androgen by inhibiting the key enzme CYP17 in the androgen synthesis pathway.However,even patients who were initially sensitive to abiraterone will gradually develop resistance to abiraterone after a period of treatment.As for the mechanism leadincg to resistance to abiraterone.it has not、yet been fully studied.It seems unrealistic to conduct abiraterone-resistant research on patients.At present,there is no construction of a PC-3 abiraterone-resistant cell line for prostate cancer.Therefore,in order to further advance the abiraterone resistance mechanism the study,the purpose of this study is to:(1)Establishment of a human-prostate cancer PC-3 cell abiraterone-resistant cell line,laying the foundation for future research;(2)Detection of drug resistance of drug-resistant cells and initial exploration of the cause of drug resistance[Methods]:(I1)A PC-3 abiraterone-resistant cell line was obtained by gradually increasing the concentration of the drug;(2)The IC50 of PC-3 parental strain and PC-3 resistant strain was detected by CCK-8 method,and the drug resistance index RI was calculated.(3)The proliferation ability of PC-3 parent strain and PC-3 resistant strain was compared using the CCK-8 method for proliferation experiments;(4)Flow cytometry was used to detect the cell cycle and apoptosis of PC-3 parental strain and PC-3 resistant strain;(5)The expression difference of related drug resistance genes was detected by real-time fluorescent quantitative PCR.[Results]:(1)After 7 months of drug induction,a abiraterone-resistant cell line of prostate cancer PC-3 cells uwith a drug resistance index of 1.56 was obtained;(2)The doubling time of PC-3 resistant strains was shorter than that of PC-3 parental strains;(3)The number of PC-3 resistant strains in S phase increased compared with PC-3 parental strain,and the number of cells in G1 phase and G2/M phase decreased;PC-3 resistant strains have more apoptotic cells than PC-3 parental strains;(4)Up-regulation of PC-3 resistant strains AR,AR-V7,ErbB2,hnRNPF and CYP17A1.[Conclusion]:The human abalone-resistant PC-3 cell abiraterone-resistant cell line was successfully established.The PC-3 drug-resistant strain grew faster than the PC-3 parental strain,and the growth was more active,and the expression of related drug resistance genes was up-regulated.