Effects of compound daqiqi decoction combined with cisplatin on inhibition of ovarian cancer skov3 cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the inhibitory effect of compound Daqiqi decoction(CDQD) combined with cisplatin on subcutaneously transplanted ovarian cancer in nude mice and its related mechanisms. METHODS: The 60 subcutaneously transplanted model of nude mice was established with human ovarian cancer cell line SKOV3, and divided into 6 groups randomly, each group of 10 nude mice, which were model group that was treated with saline, CDQD low dose group with the CDQD dosage of 15.16 g•kg-1, CDQD medium dose group with the CDQD dosage of 30.33 g•kg-1, CDQD high dose group with the CDQD dosage of 60.66 g•kg-1, cisplatin group with the DDP dosage of 3 mg•kg-1 and combined group that was treated with the CDQD dosage of 30.33 g•kg-1 and the DDP dosage of 3 mg•kg-1. Cisplatin was administered once every 3 d, and the remaining drugs were administered once a day. Then,the tumor-bearing mouse model was given the corresponding drugs for 14 consecutive days, and the tumor volume was measured every 3 d. After the end of treatment, the tumor was removed and weighed. The morphology of the tumor cells were observed by HE staining. The apoptosis of tumor cells was detected by TUNEL method. The mRNA and protein expression of miR939 and STAT3 and VEGFA and EGFR in tumor tissues were detected by real-time fluorescence quantitative PCR and Western-blot. RESULTS: The tumor volume and the tumor weight of the treated groups were all decreased(P<0.01). Compared with the model group, the tumor volume and tumor weight of the combined group were less than those of the other groups(P<0.01), and the apoptosis rate of the combined group was significantly higher than other groups(P<0.01).The expression of miR939 and STAT3 and VEGFA were down-regulated and the expression of EGFR were up-regulated in the treatment groups. Compared with the model group, the expression of MiR-939, STAT3 and VEGFA were down-regulated and the expression of EGFR was increased in the treatment group. MiR-939, STAT3, VEGFA expression in the combined group was the lowest(P<0.05), and the EGFR expression was highest(P<0.05). CONCLUSION: Studies have shown that CDQD can inhibit ovarian cancer subcutaneously transplanted tumor in nude mice, and its mechanism may be related to inhibition of MiR-939/STAT3 pathway activation, down-regulation of VEGFA, and up-regulation of EGFR expression. The inhibitory effect of CDQD on ovarian cancer tissues has a concentration dependence. And the combination of CDQD and DDP can enhance the anti-tumor effect of DDP and reduce the side effects of DDP on tumor-bearing mice.