Experimental study of 1integrin antisense oligodeonucleotide in combination with cisplatin for human ovarian carcinoma xenograft in nude mice

Objective:To explore the feasibility of antisense oligodeoxynucleotide(ASODN) targeting 1integrin gene for treatment of human ovarian cancer in nude mice.Methods:Routinely cultured SKOV3 cells were subcutaneously implanted in the nude mice to establish xenograft animal model.The 32 tumor-bearing mice were randomly divided into ASODN group(A group),ASODN combined with DDP group(A+D group),DDP group and physiological saline control group(NS group)(n=8 in each ).Drug treatment was started after randomization.After 1integrin ASODN mediated by cytofectin was directly injected into the xenograft,the volume and weight of the tumor mass were detected,and then the tumor growth inhibitory rate was calculated.Reverse transcription-polymerase chain reaction(RT-PCR) and immunochemohistology assay were used to detect the expression level of 1integrin mRNA.Results:In the A group,the tumor volume and tumor anticancer efficacy were(316.1021.77) mm3 and 48.15%,respectively.The tumor growth inhibitory rate and tumor volume were significantly different between the NS group and the A group(P0.01).In the A+D group,the tumor volume reduced to (178.7040.67)mm3 and the tumor anticancer efficacy was enhanced to 70.37%,which were significantly different compared with those of the DDP group and other controls(P0.05 to P0.01).Significant down-regulation of 1integrin mRNA expression in the tumor tissues of the A group and A+D group was detected by RT-PCR and immunochemohistology assay(P0.01).Conclusions:Singly use of 1integrin ASODN or combined with DDP can effectively inhibit the growth of human ovarian carcinoma xenograft in nude mice by direct intra-tumoral injection.The anticancer efficacy may be associated with the down regulation of 1integrin expression.ASODN targeting 1integrin gene can be a supportive therapy to the ovarian cancer.