Objective To investigate the effects of propofol and remimazolam on the proliferation of prostate cancer cells and related mechanisms.Methods Human prostate cancer cell lines DU145 and PC3 were selected and cultured to the logarithmic growth phase.Cells were randomly divided into four groups:the control group(group C),the propofol group(group P),the remimazolam group(group R),and the propofol combined with remimazolam group(group PR).Group C was cultured with complete medium,groups P and R were cultured with semi-inhibitory concentrations(IC50)of propofol and remimazolam(IC50 of propofol in DU145 and PC3 cells were 120 μg/ml and 100 μg/ml,IC50 of remimazolam were 500 μmol/L and 400 μmol/L),and DU145 cells in group PR were co-cultured with low concentration propofol 100 μg/ml and remimazolam 400 μmol/L,PC3 cells were co-cultured with low concentrations of propofol 80 μg/ml and remimazolam 300 μmol/L.The absorbance of 0,6,12,24,and 36 hours after incubation of the wells was determined by CCK-8.The number of colonies of 14 days after incubation was calculated by colony for-mation assay.qPCR and Western blot were used to detect the expression of mRNA and protein of c-Myc and cyclin D1.The key target genes of propofol and remimazolam on prostate cancer cells were identified by net-work pharmacological analysis,and the expression of mRNA and protein of the target gene were detected by qPCR and Western blot.Results Compared with group C,the absorbance at 36 hours,the number of colo-nies and the expression of mRNA and protein of c-Myc and cyclin D1 were decreased significantly in groups P,R,and PR of DU145 and PC3 cells(P＜0.05).Compared with group P,in DU145 cells,the absor-bance at 36 hours and the expression of mRNA of cyclin D1 in groups R and PR were significantly reduced,the expression of mRNA of c-Myc in group R was increased significantly,the number of colonies and the ex-pression of protein of c-Myc in group PR were significantly reduced(P＜0.05).In PC3 cells,the expres-sion of mRNA and protein of cyclin D1 in the group R were significantly reduced,the absorbance at 36 hours and the expression of mRNA and protein of c-Myc and cyclin D1 in group PR were significantly re-duced(P＜0.05).Compared with group R,the number of colonies and the expression of mRNA and pro-tein of c-Myc in group PR of DU145 and PC3 cells were significantly reduced(P＜0.05).The results of network pharmacological analysis showed that the common target of propofol,remimazolam and prostate cancer was signal transducer and activator of transcription 3(STAT3).Compared with group C,the expres-sion of mRNA and protein of STAT3 were decreased significantly in groups P,R,and PR in DU145 and PC3 cells(P＜0.05).Compared with group P,in DU145 cells,the expression of mRNA and protein of STAT3 were increased significantly in group R,the expression of protein of STAT3 was increased signifi-cantly in group PR(P＜0.05).In PC3 cells,the expression of mRNA of STAT3 was decreased significant-ly in group R(P＜0.05).Compared with group R,the expression of protein of STAT3 was decreased sig-nificantly in group PR in DU145 cells(P＜0.05).Conclusion The proliferation of prostate cancer cells can be inhibited by propofol and remimazolam alone or synergistically and they can also reduce the expres-sion of mRNA and protein of c-Myc and cyclin D1,the mechanism may be related to the inhibition of ex-pression of STAT3 which is the member of the HIF-1α pathway.