rhTRAIL对小鼠乳腺癌的抑制作用  

The inhibitory action of rhTRAIL on mouse breast carcinoma

作　　者：陈伟莉[1,2] 牟旭鹏[1] 马杰[1] 刘韦[1,3] 颜炜群[1] 

机构地区：[1]吉林大学药学院生物工程教研室,吉林长春130021 [2]黑河学院教育系,黑龙江黑河164300 [3]陕西超英生物科技有限公司,陕西西安710000

出　　处：《中国病理生理杂志》2009年第3期480-483,共4页Chinese Journal of Pathophysiology

基　　金：国家高技术研究发展计划(863计划)资助项目(No.2004AA205020);黑龙江省教育厅科学技术研究资助项目(No.11533044)

摘　　要：目的:探讨重组人肿瘤坏死因子相关凋亡诱导配体(rhTRAIL)对小鼠乳腺癌的抑制作用。方法:将5×109cells/L对数生长期的小鼠乳腺癌细胞D2F2接种于BALB/c小鼠右上肢皮下,每只接种0.2mL(1×106个细胞),随机分为5组。空白对照组:PBS0.2mL;rhTRAIL低、中、高剂量组:剂量分别为2.5mg/kg、5.0mg/kg、10.0mg/kg;阳性药物组:环磷酰胺30.0mg/kg。各组均采用腹腔注射,每天1次,共15d。每天小鼠称重记录,每3d观察肿瘤的生长情况并用游标卡尺测定肿瘤的长径和短径,计算肿瘤体积和抑瘤率。停药后处死小鼠,取瘤进行肿瘤组织光镜和电镜观察。同时流式细胞仪检测经不同浓度rhTRAIL作用后细胞凋亡及细胞周期变化。结果:与空白对照组相比,rhTRAIL2.5mg/kg、5.0mg/kg、10.0mg/kg(低、中、高)剂量组的肿瘤重量和体积明显低于空白对照组(P<0.01),且rhTRAIL低、中、高剂量组的肿瘤重量和体积随药物浓度的增加而降低(P<0.01)。rhTRAIL2.5mg/kg、5.0mg/kg、10.0mg/kg(低、中、高)剂量组肿瘤细胞既有坏死也有凋亡样改变,肿瘤组织破坏面积大,很多区域看不到正常的肿瘤细胞,可见凋亡小体。流式细胞仪检测结果显示rhTRAIL蛋白可诱导D2F2细胞凋亡,0.25mg/L、0.5mg/L、1.0mg/L组细胞凋亡率分别为7.56%、21.37%、27.16%,凋亡率随剂量增大而升高(P<0.05)。结论:rhTRAIL可诱导小鼠乳腺癌细胞D2F2凋亡并有大量的乳腺癌细胞坏死,rhTRAIL对小鼠乳腺癌细胞D2F2具有抑制作用。AIM ： To explore the inhibitory action of recombinant human tumor necrosis factor - related apopto- sisinducing ligand（rhTRAIL） on mouse breast cancer. METHODS： Each mouse was inoculated 0. 2 mL （1 × 10^6） D2F2 cells subcutaneously in the right lower limb and they were divided into five groups randomly. The control group was infused PBS 0.2 mL, while the lowdose, medium, high groups received purified rhTRAIL 2. 5 mg/kg, 5.0 mg/kg, 10. 0 mg/kg, respectively, the positive group was administered cyclophosphamide 30.0 mg/kg. Every group was operated by peritoneal injection once a day for fifteen days. The mice were weighed every day. The growth state was viewed and the size of the tumor was measured every 3 d to calculate the tumor volume and tumor suppression rate. All mice were killed after 15 d. The pathologic changes of the tumor were observed under light - microscopy and electronic microscopy. The cell cycle and apoptosis index of D2F2 cells were analyzed by flow cytometry. RESULTS： The body weight and tumor volume in low -dose, medium, high groups were lower than those in control group and the restriction effect was more significant than that in the control group （ P 〈 0. 01 ）. The body weight and tumor volume in low - dose, medium, high groups decreased with the increase in rhTRAIL concentration. The difference was significant （P 〈 0. 01 ）. Both apoptosis and necrosis of tumor cells were observed in low - dose, medium, high groups. The area of cell apoptosis was large and most area didn＇t have tumor cells but only apoptotic bodise. The results of flow cytometry showed that rhTRAIL induced the apoptosis of D2F2 cells, and the apoptosis rates were 7.56 %, 21.37 %, 27. 16 % respectively when rhTRAIL doses were 0. 25mg/L, 0. 5 rag/L, 1.0 mg/L. Significant differences among three groups were observed （P 〈0. 05）. CONCLUSION： rhTRAIL induces apoptosis in mouse breast cancer cells and even the necrosis of tumor cells, rhTRAIL has significant effect on inhibiting the growth of D2F2

关 键 词：肿瘤坏死因子相关凋亡诱导配体 乳腺肿瘤 细胞凋亡 

分 类 号：R737.31[医药卫生—肿瘤]