Anti-tumor mechanism of norcantharidin for the implanted tumors of human gallbladder carcinoma in nude mice in vivo
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF SURGERY
- Issue:
- 9
- DOI:
- 10.3760/j.issn.0529-5815.2006.09.012
- Key Word:
- 胆囊肿瘤;斑蝥素;动物;实验
Abstract： 目的探讨去甲斑蝥素(NCTD)对荷瘤裸鼠胆囊癌移植瘤的抗癌作用机制.方法在建立裸鼠胆囊癌移植瘤动物模型的基础上进行肿瘤增殖、侵袭、转移体内干预实验,实验分空白对照、氟尿嘧啶、NCTD、NCTD+氟尿嘧啶4组.6周末应用链霉素亲和生物素复合物(SABC)法检测移植瘤增殖细胞核抗原(PCNA)、Ki-67、细胞周期素D1(cyclin D1)、p27、Bcl-2蛋白,逆转录PCR(RT-PCR)检测PCNA、cyclin D1、p27、Bcl-2、Bax、存活素(Survivin)基因mRNA.HE染色观察瘤周癌细胞浸润、侵袭,解剖显微镜下观察肺组织转移瘤结节,并采用SABC和RT-PCR检测nm23、金属蛋白酶2(MMP2)及其组织抑制剂(TIMP2)蛋白和mRNA.结果NCTD组增殖相关PCNA、Ki-67、cyclin D1蛋白表达下降,p27蛋白表达上升;PCNA mRNA、cyclin D1mRNA表达下降,p27 mRNA表达增高.NCTD组凋亡相关Bcl-2蛋白表达下降;Bcl-2 mRNA、Survivin mRNA表达下降,Bax mRNA表达增高.NCTD显著减少荷瘤鼠移植瘤的瘤周癌细胞浸润和肺转移结节(P＜0.01);NCTD组转移相关MMP2蛋白表达下降,nm23、TIMP2蛋白表达上升;nm23-H1mRNA、TIMP2 mRNA表达增高.结论NCTD抑制荷瘤裸鼠胆囊癌移植瘤增殖、侵袭和转移的机制可能与NCTD干扰胆囊癌移植瘤细胞周期,抑制细胞增殖,诱导细胞凋亡,阻止细胞迁移运动,以及影响细胞增殖、细胞周期调控、细胞凋亡、细胞基质溶解和转移相关基因蛋白表达有关.
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