摘要
目的:探讨泌乳素诱导蛋白(prolactin-inducible protein,PIP)表达下调对三阴性乳腺癌(triple negative breast cancer,TNBC)MDA-MB-453细胞在裸鼠体内成瘤的影响。方法:采用脂质体将PIP siRNA转染至乳腺癌MDA-MB-453细胞,蛋白质印迹法检测PIP的表达下调情况。采用4周龄BALB/c雌性裸鼠,建立乳腺癌MDA-MB-453细胞裸鼠皮下种植瘤模型,瘤内注射siRNA-脂质体混悬液,观察PIPsiRNA对肿瘤生长的影响。采用免疫组织化学法检测肿瘤组织中Cyclin D1和VEGF的表达情况。结果:PIP表达下调后,其在裸鼠体内成瘤能力明显降低,肿瘤平均体积空白对照组为(1 075±65)mm3,阴性对照组为(1 095±72)mm3,实验组为(473±56)mm3,空白对照组与阴性对照组差异无统计学意义,P=0.719,空白对照组与实验组、实验组与阴性对照组差异均有统计学意义,P<0.001。空白对照组肿瘤平均体质量为(908±86)mg,阴性对照组为(889±64)mg,实验组为(272±30)mg,空白对照组与阴性对照组差异无统计学意义,P=0.738,空白对照组与实验组、实验组与阴性对照组差异均有统计学意义,P<0.001。肿瘤生长抑制率为71.1%。免疫组化结果显示,PIP表达下调的肿瘤组织中Cyclin D1的相对表达量空白对照组为1 535±78,阴性对照组为1 594±123,实验组为367±72,空白对照组与阴性对照组差异无统计学意义,P=0.472,空白对照与实验组、实验组与阴性对照组差异均有统计学意义,P<0.001。VEGF的相对表达量空白对照组为4 270±558,阴性对照组为4 365±324,实验组为1 286±292,空白对照组与阴性对照组差异无统计学意义,P=0.758,空白对照与实验组、实验组与阴性对照组差异均有统计学意义,P<0.001。结论:下调PIP基因表达可明显抑制乳腺癌MDA-MB-453细胞体内成瘤能力,提示PIP可能在乳腺癌发生和发展中发挥重要作用。
OBJECTIVE：To investigate the effects of prolactiwinducible protein （PIP） downregulatng the growth of human MDA-MB-453 breast cancer xenograft in nude mice. METHODS：PIP siRNA was transfected into human triple-neg ative breast cancer MDA MB-453 cells through liposome. Western blot was employed to confirm the downregulated ex- pression of PIP. Four-week-old BALB/c female nude mice were adopted to establish a subcutaneously tumor-bearing model. The inhibitory effects of siRNA on tumor growth were assessed by intraturotumoralinjection of siRNA-liposome com plex. Immunohistochemical staining was performed to examine the expressions of Cyclin D1 and VEGF. RESULTS：Knock down of PIP obvioulsy inhibited the growth of breast cancer xenograft in nude mice. The tumor volume in blank-control, negative-control and experimental group was （1 075±65） mm3 ,（1 095±72） mm3 and （473±56） mm3. There was no sig nificant difference between the blank control and negative control （P=0. 719）. There was significant difference between the experimental group and the blank control and the negative control group （P〈0. 001）. The tumor mass in blank-con- trol,negative-control and experimental group was （908 ± 86） rag, （889± 64） mg and （272 ±30） mg respectively.There was no significant difference between the blank control and negative control group （P=0. 738）. There was signifi cant difference between the experimental group and the blank control and the negative control group （P〈0. 001）. Inhibi tion ratio of tumor volume reached 71. 1%. Moreover,PIP siRNA markedly downregulated the expressions of Cyclin D1 and VEGF. The expression of Cyclin D1 in blank-control, negative-control and experimental group was 1 535±78,1 594±123 and 367 ± 72 respectively. There was no significant difference between the blank control and negative control（P = 0. 472）. There was significant difference between the experimental group and the blank control and the negative control group （P〈%0. 001）. The expression of VEGF in blank-control, negative-control and experimental group was 4 270 ± 558, 4 365±324 and 1 286±292 respectively. There was no significant difference between the blank control and negative con trol （P=0. 758）. There was significant difference between the experimental group and the blank control and the negative control group （P〈0. 001）. CONCLUSION.. Reduced PIP expression in MDA-MB-453 cells can inhibit breast cancer growth in vivo, which suggests that PIP plays an important role in the tumorigenesis and progression of breast cancer cells.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2014年第4期260-264,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家十二五重大新药创制平台子课题(2012ZX09303016-002)
