桂枝茯苓丸联用顺铂紫杉醇化疗提高卵巢癌多药耐药模型裸鼠生存率  

Guizhi Fuling Wan Combined with Cisplatin / Paclitaxel Chemotherapy Enhance Survival Rate of Ovarian Cancer Multidrug Resistance Tumor-bearing Mice

作　　者：郭晓娟[1] 韩立[1] 杨雷[1] 臧文华[1] 卞华[1] 

机构地区：[1]南阳理工学院张仲景国医国药学院,南阳473004

出　　处：《科学技术与工程》2016年第20期120-124,共5页Science Technology and Engineering

基　　金：河南省科技厅基础与前沿项目(152300410179)资助

摘　　要：研究桂枝茯苓丸逆转人卵巢癌耐顺铂细胞株(SKOV3/DDP)肿瘤模型的耐药作用及其对荷瘤BALB/c裸鼠生存率的影响,探讨其可能的作用机制。采用Cell Counting Kit-8试剂盒检测SKOV3/DDP对顺铂和紫杉醇的耐药性;采用SKOV3/DDP细胞建立卵巢癌耐药肿瘤模型,模型BALB/c裸鼠随机分为桂枝茯苓丸浓缩液16 g·kg^(-1)·d^(-1)(高)、8 g·kg^(-1)·d^(-1)(中)、4g·kg^(-1)·d^(-1)(低)剂量(中药组)、顺铂/紫杉醇组(化疗组)、低剂量桂枝茯苓丸与化疗联用组(中西联用组)和空白对照组,检测各处理组的抑瘤率。观察各组BALB/c裸鼠的生存情况;并采用荧光定量PCR检测各组肿瘤组织中MDR1 mRNA的相对表达。结果是SKOV3/DDP细胞对顺铂和紫杉醇的耐药倍数分别为4.13倍和3.85倍。随着桂枝茯苓丸浓缩液剂量的增加,抑瘤作用增强,裸鼠生存率提高,肿瘤组织MDR1 mRNA表达相对于对照组逐渐下降。西药化疗组在耐药模型裸鼠中的抑瘤效果高于中药组,中西药联用后抑瘤效果显著高于西药化疗组;与其他各组相比,西药化疗组的裸鼠平均体重明显下降,差异均具有显著性(P<0.05,P<0.01)。中西联用组裸鼠生存率高于桂枝茯苓丸低剂量组和西药化疗组。西药化疗组MDR1mRNA表达相对于对照组显著增加,中西药联用组MDR1 mRNA表达相对于对照组显著下降,差异均具有显著性(P<0.05,P<0.01)。说明桂枝茯苓丸能够逆转SKOV3/DDP耐药性卵巢癌模型裸鼠的耐药性,提高裸鼠生存率,其机制可能与抑制MDR1 mRNA表达有关。To study the reversal effect of Guizhi Fuling Wan( GFW) and its effect on survival rate in BALB /c xenograft nude mice generated with SKOV3 / DDP cells and to explore the possible mechanism,The resistance of SKOV3 / DDP cells to cisplatin or paclitaxel was tested by Cell Counting Kit-8. A resistant ovarian cancer BALB / c xenograft nude mice model was generated from SKOV3 / DDP cells. The nude mices were randomly divided into six groups: GFW high( 16 g·kg^(-1)·d^(-1)),middle( 8 g·kg^(-1)·d^(-1)) and low( 4 g·kg^(-1)·d^(-1)) doses( Traditional Chinese medicine,TCM) groups,cisplatin / paclitaxel chemotherapy group,low dose of GFW combined with cisplatin / paclitaxel chemotherapy group( Combined group) and control group. The tumor inhibition rate( TIR) and survival rate( SR) were tested in the different groups. The relative changes of MDR1 mRNA in tumor tissues were examined by a real-time quantitative PCR. It is resulted that resistance times of SKOV3 / DDP cells to cisplatin or paclitaxel were 4. 13 and 3. 85,respectively. The TIR and SR were increased with the dose of GFW increased. A similar effect was observed for the relative changes of the MDR1 mRNA level in tumor tissues compared with control group. The TIR in the chemotherapy group is higher than that of TCM groups. The TIR in the combined group was higher than that of chemotherapy group. The average body weights of mice in the chemotherapy group was lower than that of other groups. The SR in combined group was higher than those of low dose of GFW group and chemotherapy group. The MDR1 mRNA level in the chemotherapy group was increased significantly compared with that of control group,the MDR1 mRNA level in the combined groups was decreased significantly compared with that of control group. All the comparative results have significant difference( P < 0. 05,P < 0. 01). Conclusions: GFW can reverse the resistance and increase SR in BALB / c xenograft nude mice generated with SKOV3 / DDP cells,the mechanism may be related to inhibition of MDR1 mRNA.

关 键 词：桂枝茯苓丸 卵巢癌 多药耐药 生存率 

分 类 号：R285.5[医药卫生—中药学]