摘要
目的:探讨去甲斑蝥素(NCTD)对荷瘤裸鼠胆囊癌移植瘤抑制作用。方法:建立荷瘤裸鼠胆囊癌模型,应用NCTD对该动物模型进行移植瘤增殖、生长的抑制实验,观察并测量荷瘤鼠移植瘤大小、计算抑瘤率,应用流式细胞术和免疫组化等观测移植瘤细胞的细胞周期,凋亡率,PCNA,Ki-67,Cyclin D1,p27基因蛋白表达。结果:NCTD的半数致死量(LD50)为139．96 mg·kg-1,应用1／5LD50。即可使NCTD组裸鼠移植瘤生长减缦[(5．6±s 0．4)cm3与对照组(9．8±0．6)cm3比较,P<0．011,抑瘤率上升(43±8)％;S期细胞减少、细胞凋亡率上升;免疫组化检测显示,NCTD组PCNA,Ki-67,cyclin D1表达下降,p27表达上升,与氟脲嘧啶(FU) 联合应用时作用明显。结论:NCTD可明显抑制荷瘤裸鼠胆囊癌移植瘤的增殖和生长,与FU合用呈协同效应以加强其抗癌作用;其机制可能与NCTD干扰荷瘤鼠胆囊癌移植瘤细胞周期,抑制细胞增殖,诱导细胞调亡以及改变细胞增殖、细胞周期调控相关基因蛋白表达有关。
AIM： To explore the effect in vivo of planted tumors of human gallbladder carcinoma in nude norcantharidin （NCTD） on proliferation and growth of immice. METHODS： Animal model simulating human gallbladder carcinoma was created by subcutaneous implantation of cultured GBC-SD cell lines into nude mice. Mice used in experiments were randomly divided into four groups and were taken different treatments. Tumor dimensions, tumor inhibitory rates of each group were respectively evaluated. Flow cytometry was used to measure the cell cycle and the induction of apoptosis. Immunohistochemistry was taken to determine the expressions of PCNA, Ki-67, cyclin D1 and p27 gene proteins in each paraffin section of every group. RESULTS：LD50 of NCTD was 139.96 mg·kg^-1. Volume of implanted tumors of NCTD group vs control group [（5.6 ± s 0.4） cm^3 vs （9.8 ±0.6） cm^3, P 〈 0.01] in nude mice after treatment showed the former was smaller than that of the control group, but with increase of tumor inhibitory rate （43± 8） %. The flow cytometric profiles in NCTD group and NCTD＋FU group revealed decrease percentage of implanted tumor cells in the S phase,simul taneously with the increase rate of cell apoptosis. The expressions of PCNA, Ki-67, cyclin D1 were significantly decreased together with significant increase of expression p27, in paraffin sections of NCTD group. CONCLUSION： NCTD can inhibit the proliferation and growth of human cholecystic carcinoma ceils in implanted tumor of nude mice and further intensified effect could be achieved with combination of FU. Its anti-tumor mechanism might be correlated with inhibition of cell proliferation, blockage of cell cycle,induction of cell apoptosis, alteration of the expression of proliferation and cycle control-related gene proteins such as PCNA, Ki-67 ,cyclim D1 ,p27.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2006年第2期98-103,共6页
Chinese Journal of New Drugs and Clinical Remedies
