复方大七气汤联合顺铂对卵巢癌SKOV3细胞的抑制作用  

Effects of Compound Daqiqi Decoction Combined with Cisplatin on Inhibition of Ovarian Cancer SKOV3 cells

作　　者：邱文平[1] 兰楠 严茂铭 易均路 陈蓉[1] QIU Wen-ping;LAN Nan;YAN Mao-ming;YI Jun-lu;CHEN Rong(Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University Chongqing 400016, China;Chongqing City Dianjiang County Traditional Chinese Medicine Hospital, Chongqing 408317, China;Chongqing Jiulongpo District Hospital of Traditional Chinese Medicine, Chongqing 400000, China)

机构地区：[1]重庆医科大学中医药防治代谢性疾病重庆市重点实验室,重庆400016 [2]重庆市垫江县中医院,重庆408317 [3]重庆市九龙坡区中医院,重庆400000

出　　处：《中国药学杂志》2019年第5期373-381,共9页Chinese Pharmaceutical Journal

摘　　要：目的探讨研究复方大七气汤(compound Daqiqi decoction,CDQD)联合顺铂对卵巢癌裸鼠皮下移植瘤抑制作用及其相关机制。方法采用人卵巢癌细胞株SKOV3构建60只裸鼠皮下移植瘤模型,随机分为6组,每组10只,分别为模型组(生理盐水),CDQD低剂量组(15.16 g·kg^(-1)),CDQD中剂量组(30.33 g·kg^(-1)),CDQD高剂量组(60.66 g·kg^(-1)),顺铂组(DDP,3mg·kg^(-1)),联合组(30.33 g·kg^(-1)CDQD+3 mg·kg^(-1)DDP),顺铂3 d·次^(-1),其余1 d·次^(-1),连续给药14 d,每3 d测瘤体积,治疗结束后剥取瘤体,称瘤重并计算抑瘤率,绘制肿瘤生长曲线。采用HE染色法观测各组肿瘤细胞形态,TUNEL法检测肿瘤组织细胞凋亡情况,实时荧光定量PCR和Western-blot检测肿瘤组织中miR-939、信号转导子与转录激活子3(STAT3)、血管内皮生长因子A(VEGFA)和血管内皮生长因子受体(EGFR)mRNA及蛋白的表达。结果与模型组相比,治疗组瘤体积、瘤重均减小(P<0.01),联合组瘤体积和瘤重均小于其余各组(P<0.01),联合组细胞凋亡率明显高于其余各组(P<0.01)。与模型组相比,治疗组中MiR-939、STAT3与VEGFA表达均下调,EGFR表达上升,其中联合组MiR-939、STAT3、VEGFA表达最低(P<0.05),EGFR表达最高(P<0.05)。结论 CDQD对卵巢癌裸鼠皮下移植瘤具有抑制作用,其机制可能与抑制MiR-939/STAT3通路激活,下调VEGFA、上调EGFR表达有关。CDQD对卵巢癌组织的抑制作用具有浓度依耐性,并且与DDP联合用药能增强DDP抗瘤作用,减轻DDP对荷瘤鼠的毒副作用。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 l

关 键 词：卵巢癌 复方大七气汤 顺铂 增殖 裸鼠 SKOV3细胞 

分 类 号：R969.1[医药卫生—药理学]