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银杏外种皮提取物抗小鼠肺癌转移及其机制研究

Study on anti-metastasis effect of Ginkgo biloba exocarp extracts on metastasis of C57BL/6J mice Lewis lung cancer and its mechanism

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【作者】 许爱华沈婷婷许月陈华圣

【Author】 XUAi-hua,SHEN Ting-ting,XUYue,CHEN Hua-sheng (Medical College of Yangzhou University,Yangzhou 225001,Jiangsu,China)

【机构】 扬州大学医学院

【摘要】 目的研究银杏外种皮提取物(GBEE)对小鼠Lewis肺癌转移的抑制作用及其作用机制。方法建立C57BL/6J小鼠Lewis肺癌转移模型,随机分为模型对照组、阳性对照组及GBEE高、中、低3个治疗组,另设不接种肿瘤的正常对照组,分别ig给予等体积生理盐水(NS)、替加氟80mg·kg-1、GBEE200,100和50mg·kg-1,正常对照组亦ig等体积NS,皆每日一次,连续给药15d。于d16解剖显微镜下观察肺表面转移灶数,计算肺癌转移率和抗转移率;放射免疫法测定血清Ⅳ型胶原(ColⅣ)及透明质酸(HA)的含量;免疫组织化学技术检测移植瘤细胞CD44及nm23-H1的表达。结果模型对照组小鼠Lewis肺癌转移率为70%,GBEE高、中、低3个治疗组小鼠Lewis肺癌转移率明显低于对照组,分别为40%、30%及50%;与模型对照组比较,GBEE各治疗组小鼠肺癌转移灶明显减少,抗转移率分别为58.33%、87.50%及41.67%,小鼠血清中ColⅣ及HA的含量明显降低,皆具有极显著性差异(P<0.01);GBEE显著抑制小鼠Lewis肺癌移植瘤细胞CD44的表达,并促进nm23-H1的表达,皆具有统计学意义(P<0.05或P<0.01)。结论 GBEE对Lewis肺癌转移模型小鼠具有抗肿瘤转移作用,其机制涉及对肿瘤转移抑制基因nm23-H1表达的诱导以及对肿瘤细胞粘附分子CD44表达的抑制,并伴有小鼠血清ColⅣ和HA含量的降低。

【Abstract】 OBJECTIVE To study the anti-metastasis effect of Ginkgo biloba exocarp extracts(GBEE)on metastasis of C57BL/6J mice Lewis lung cancer and its mechanism.METHODS The establishments of C57BL/6J mice with Lewis lung metastasis model were randomly divided into model control,positive control and GBEE(high,medium and low)treatment groups.In addition,the normal control group was built without inoculating tumor cell suspension fluid.The mice in positive control group were ig tegafur 80 mg ? kg-1,the GBEE(high,medium and low)treatment groups were respectively ig GBEE(200,100 or 50)mg ? kg-1,the model control group and the normal control group were both ig equal volume of saline(NS),once a day for 15d. d16,the metastatic tumor foci on lung surface in mice were counted to calculate the rate of cancerometastasis and anti-metastasis of tumor on lung surface.Radioimmunoassay was performed to observe the content of Ⅳ collagen(Col Ⅳ )and hyaluronic acid(HA)in serum,immunohistochemistry method was utilized for measuring the expressions of CD44 and nm23-H1 of transpiantated tumors.RESULTS The occurrence rate of metastases of Lewis lung cancer in model control group was 70%.Compared with that,the occurrence rates of metastases in GBEE(high,medium and low)3 treatment groups all have significantly increased,respectively were 40%,30%and 50%.The metastatic foci occurrence rates of all GBEE treatment groups on lung surface were lower than control group,the inhibition rates of metastases were 58.33%,87.50%and 41.67%.At the same time, the contents of HA and Col Ⅳ in mice serum were also significantly lower,both highly significant difference (P<0.01).GBEE also significantly inhibited the expression of CD44 in tumor cells and promoted the expression of nm23-H1,are statistically significant(P <0.05 or P <0.01).CONCLUSION GBEE has an anti-tumor metastasis activity on Lewis lung metastasis model in C57BL/6J mice,the mechanisms involved in inducing the expressions of tumor metastasis suppressor gene nm23-H1 and reducing that of tumor cell adhesion molecule CD44 in mice,accompanied by the content changes of HA and Col Ⅳ in serum.

【基金】 江苏省科技发展计划医药高技术研究基金项目(编号:BG2007609)资助~~
  • 【会议录名称】 2012全国天然药物和中药毒理、药理学交流研讨会论文集
  • 【会议名称】2012全国天然药物和中药毒理、药理学交流研讨会
  • 【会议时间】2012-07-22
  • 【会议地点】中国湖南张家界
  • 【分类号】R285.5;R734.2
  • 【主办单位】全国医药技术市场协会
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