国际妇产科学杂志 ›› 2017, Vol. 44 ›› Issue (1): 48-51.

• 论著 • 上一篇    下一篇

泰素帝对人卵巢癌SKOV3裸小鼠移植瘤的抑制作用及其与顺铂、赫赛汀联合作用的探讨

伍亚伟   

  1. 江苏省昆山市第一人民医院
  • 收稿日期:2016-05-25 修回日期:2017-01-06 出版日期:2017-02-15 发布日期:2017-03-28
  • 通讯作者: 伍亚伟 E-mail:490479342@qq.com

Anti-tumor effect of Taxotere on nude mice xenografts of human ovarian cancer SKOV3 cells and its synergistic effect of action with Cisplatin,Herceptin

  • Received:2016-05-25 Revised:2017-01-06 Published:2017-02-15 Online:2017-03-28

摘要: 目的:1.观察多西紫杉醇(Docetaxel,又名多西他赛,商品名:泰素帝 Taxotere)对人卵巢癌SKOV3细胞裸小鼠移植瘤的抑制作用,并初步探讨其作用机制;2.观察泰素帝及其联合顺铂(diammine dichloro platinum,DDP)或(和)曲妥株单抗(Trastuzumab,商品名:赫赛汀 Herceptin)对人卵巢癌SKOV3裸小鼠移植瘤的抑制差异。方法:成功建立人卵巢癌SKOV3裸小鼠移植瘤模型后,随机将荷瘤裸鼠分为8组:①顺铂组,②赫赛汀组,③泰素帝组,④顺铂+赫赛汀组,⑤顺铂+泰素帝组,⑥赫赛汀+泰素帝组,⑦顺铂+赫赛汀+泰素帝组,⑧对照组,每组4只。顺铂按3mg/kg、赫赛汀按30mg/kg、泰素帝按5mg/kg每周一次经尾静脉用药,连续六周,每周测量一次小鼠肿瘤的长、短径及小鼠体重,用药结束后一周处死小鼠,计算抑瘤率,肿瘤组织HE染色观察细胞凋亡、Tunel技术检测凋亡指数、免疫组化技术检测肿瘤组织中Ki-67的表达情况。结果:1.泰素帝能明显抑制人卵巢癌SKOV3细胞裸小鼠移植瘤的生长,且分别与顺铂、赫赛汀联合后对肿瘤生长的抑制作用更明显,而顺铂+赫赛汀+泰素帝三联组对肿瘤生长的抑制作用最明显;2. 泰素帝单药组肿瘤细胞凋亡指数较对照组显著升高,且分别与顺铂、赫赛汀联合后肿瘤细胞凋亡指数更高,而顺铂+赫赛汀+泰素帝三联组肿瘤细胞凋亡指数最高;3. 泰素帝单药组肿瘤组织中Ki-67的表达率较对照组显著下降,且分别与顺铂、赫赛汀联合后肿瘤组织中Ki-67的表达率下降更明显,而顺铂+赫赛汀+泰素帝三联组肿瘤组织中Ki-67的表达率下降最明显。结论:1.泰素帝能够有效抑制人卵巢癌SKOV3裸小鼠移植瘤的生长。其可能的机制是通过下调Ki-67等的表达而抑制肿瘤的增殖活性,并诱导肿瘤细胞凋亡。2.泰素帝分别与顺铂、赫赛汀间具有协同作用,而泰素帝、顺铂、赫赛汀三药联合应用能更有效的抑制肿瘤生长。

关键词: 卵巢癌, 泰素帝, 顺铂, 赫赛汀, 抑制作用

Abstract: Objective:1.To study the anti-tumor effect of taxol drugs Taxotere on nude mice xenografts of human ovarian cancer SKOV3 cells and explore its possible mechanism; 2.To compare the anti-tumor effect of Taxotere with the combination of DDP,Herceptin on nude mice xenografts of human ovarian cancer SKOV3 cells.Methods:An animal model with human ovarian cancer SKOV3 cells involved in nude mice was established and the mice were randomized into 8 groups: ①DDP group,②Herceptin group,③Taxotere group,④DDP plus Herceptin group,⑤DDP plus Taxotere group,⑥Herceptin plus Taxotere group,⑦DDP plus Herceptin plus Taxotere group,⑧NS group,There are 4 mice in every group. The mice were administrated respectively with Cisplatin(3mg/kg)、Herceptin (20mg/kg)、Taxotere(5mg/kg) via caudal vein injection once a week for consecutive six weeks. The size of the tumor and mice weight were measured weekly, then the mice were killed a week after last treatment. The inhibition ratio of tumor growth was calculated and tumor tissues were observed by using HE staining. The apoptotic index was analyzed by using Tunel technique. The Ki-67 in xenograft tumors were analyzed by using immunohistochemical staining.Results:Taxotere can significantly inhibit the growth of xenografts of human ovarian cancer SKOV3 cells in nude mice, and the inhibition effect is more prominent when it was joint with Cisplatin or Herceptin respectively, while the inhibition effect is the most obvious when the three drugs above is joint together; 2. The tumor cell apoptotic index of Taxotere group was significantly increased than the control group, and the apoptotic index is higher when Taxotere was joint with Cisplatin or Herceptin respectively, while the apoptotic index is the highest when the three drugs above is joint together;3. The Ki-67 ratio in xenograft tumors of Taxotere group was significantly reduced than the control group, and Ki-67 ratio in xenograft tumors is lower when Taxotere was joint with Cisplatin or Herceptin respectively, while the Ki-67 ratio in xenograft tumors is the lowest when the three drugs above is joint together.Conclusion 1.Taxotere can obviously inhibit the growth of xenografts of human ovarian cancer SKOV3 cells in nude mice; Down-regulation of Ki-67 in SKOV3 cells,and induction of tumor cell apoptosis might be one of its possible mechanisms;2.There are synergistic mechanism of combinative action of Taxotere and DDP,Herceptin respetively,while the three drugs’ combination can more effectively inhibit the growth of tumor.

Key words: Ovarian cancer, Taxotere, DDP, Herceptin, Inhibition