蝙蝠葛酚性碱对胰腺癌裸鼠移植瘤刺猬信号通路关键蛋白表达的影响  

Expression of Hedgehog signaling pathway key protein in transplanted tumor of pancreatic cancer in nude mice

作　　者：刘思莹 易娅静 于颖 仲丽丽[1] LIU Si-ying;YI Ya-jing;YU Ying;ZHONG Li-li(Department of Pathology,The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang Province,China;Basic Medical School,Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang Province,China)

机构地区：[1]黑龙江中医药大学附属第一医院病理科,黑龙江哈尔滨150040 [2]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040

出　　处：《中国临床药理学杂志》2020年第16期2432-2435,共4页The Chinese Journal of Clinical Pharmacology

基　　金：黑龙江省政府博士后基金资助项目(LBH-Z14196)。

摘　　要：目的探讨蝙蝠葛酚性碱(Phenolic alkaloids from Menisphermum dauricum,PAMD)对胰腺癌细胞株BxPC-3裸鼠移植瘤的抑制作用,并分析其对瘤组织刺猬(Hedgehog)信号通路中关键蛋白音速刺猬蛋白(Sonic hedgehog protein,Shh)、补丁蛋白(Ptched receptor,Ptch1)、平滑蛋白(Smothened protein,Smo)、胶质瘤相关致癌蛋白(Glioma-associated oncogene,Gli1)表达的影响。方法用BxPC-3细胞接种裸鼠构建胰腺癌裸鼠移植瘤动物模型;另选未接种裸鼠为空白组。将造模成功的裸鼠分为4组:模型组、阳性对照组和低、高2个剂量实验组(PAMD 10,20 mg·kg-1),每组6只;均腹腔注射,模型组和空白组腹腔注射等量0.9%NaCl。阳性对照组按5-FU 20 mg·kg-1腹腔注射给药,连续给药21 d。处死小鼠检测PAMD对胰腺癌细胞株BxPC-3裸鼠移植瘤的抑制情况;采用免疫组织化学方法检测瘤组织Hedgehog信号通路Shh、Ptch1、Smo、Gli-1的蛋白表达水平。结果给药后,阳性对照组和低、高剂量实验组的抑瘤率分别是33.05%,35.16%和56.88%。模型组、阳性对照组、低、高剂量实验组的Shh蛋白相对表达量(IOD值)指标分别为61.86±3.33,60.58±2.02,37.02±2.83和40.33±2.83;Pcth1蛋白相对表达量(IOD值)指标分别为30.13±1.93,27.73±2.16,12.64±1.43和14.80±1.95;Smo蛋白相对表达量(IOD值)指标分别为36.66±4.14,28.91±3.44,16.28±2.61和13.92±3.04;Gli-1蛋白相对表达量(IOD值)指标分别为20.26±1.09,19.39±1.77,12.64±0.99和14.19±1.13。模型组与阳性对照组比较或低、高剂量实验组与模型组比较,上述指标的差异均有统计学意义(均P<0. 05)。结论 PAMD对胰腺癌BxPC-3裸鼠移植瘤具有有效的抑制作用,降低Hedgehog信号通路中关键蛋白的表达,其机制可能是通过抑制Hedgehog信号通路的激活发挥作用。Objective To investigate the inhibitory effect of Phenolic alkaloids from Menisphermum dauricum(PAMD) on human pancreatic cancer BxPC-3 xenograft tumor in nude mice, and to analyze the effect of PAMD on the expression of key proteins of Sonic hedgehog protein(Shh),Ptched receptor(Ptch1),Smothened protein(Smo),Glioma-associated oncogene(Gli1)in Hedgehog signaling pathway of tumor tissue. Methods The nude mice were inoculated with BxPC-3 cells to establish a pancreatic cancer nude mouse xenograft animal model;non-vaccinated nude mice were selected as blank groups. After making the model successfully,nude mice were divided into 4 groups: model group,positive control group,experimental-L/-H group(10,20 mg · kg-1 of PAMD),each group had 10 mice;intraperitoneal injection was performed;model group and the blank group were given the same amount of 0. 9% NaCl intraperitoneally;positive control group was administered with intraperitoneal injection of 20 mg·kg-1 of 5-FU for 21 days. Mice were sacrificed to detect the inhibition of PAMD on pancreatic cancer BxPC-3 nude mice tumors. The expression levels of Shh,Ptch1,Smo and Gli-1 protein of the Hedgehog signaling pathway were detected by immunohistochemical methods in tumor tissues. Results After administration,the tumor inhibition rates in positive control group,experimental-L/-H group were 33. 05%,35. 16% and 56. 88%,respectively. The index of relative expression(IOD value) of Shh protein in the model group,positive control group,experimental-L/-H group were61. 86 ± 3. 33,60. 58 ± 2. 02,37. 02 ± 2. 83,40. 33 ± 2. 83;the index of relative expression(IOD value) of Pcth1 protein were 30. 13 ± 1. 93,27. 73 ± 2. 16,12. 64 ± 1. 43,14. 80 ± 1. 95;the index of relative expression(IOD value)of Smo protein were 36. 66 ± 4. 14,28. 91 ± 3. 44,16. 28 ± 2. 61,13. 92 ± 3. 04;the index of relative expression(IOD value) of Gli1 protein were 20. 26 ± 1. 09,19. 39 ± 1. 77,12. 64 ± 0. 99,14. 19 ± 1. 13. There were significant differences of the factors between model group an

关 键 词：蝙蝠葛酚性碱 胰腺癌 刺猬信号通路 

分 类 号：R28[医药卫生—中药学]