· 1076·
郑锐，等
抑制Sre酪氨酸激酶对小鼠肺转移癌的干预作用
抑制Src酪氨酸激酶对小鼠肺转移癌的干预作用郑锐"，秦晓松，李文洁"，吴
莎，康健”
EffectofSrctyrosinekinaseinhibitiononpulmonarymetastasistumorinmice ZHENG Rui', QIN Xiao - song’,LI Wen jie', WU Sha',KANG Jian
Medieal Uninersity，Shenyang 110022,Chi-
'2nd Department of Respiratory Internal Medicine, Shengjing
Hospital，Ching
na ; Department of Clinical Laboratory, Shengjing Hospital, China Medical Uninersity, Shenyang 110004, China ;' Department of Respirg-tory Internal Medicine, First Afiliated Hospital, Institute of Respiratory Disease, China Medical Unitersity,Shenyang 110001 , China.
[ Abstract] Objective: To study the effect of Src tyrosine kinase inhibition on pulmonary metastasis tumor in mice and its mechanism. Methods : For lung metastasis model, A549 cells were injected into NK cell depleted SCID mice via the tail vein. Mice were orally given every day with or without Src tyrosine kinase inhibitor to examine the effect of Sre tyrosine kinase inhibition on experimental lung metastasis. Immunohistochemistry was used to test the effect of Sre tyrosine kinase inhibition on proliferation index ( Ki67 staining) and microvessel density ( CD31 stai-ning) of experimental lung metastasis in mice. Results: A549 cells developed numerous small lesions on the surface of the lung in 3 groups,but the nodules of lung in 50mg/kg/d group was smaller than that of control group,represen ting significantly less lung weight compared to control group and 50mg/kg/d group( P < 0. 05). Treatment with 10mg/ kg/d Src tyrosine kinase inhibitor had no significant effect on the lung weight. Treatment with Sre tyrosine kinase in hibitor did not cause weight loss of mice significantly, however, inoculated A549 cells 35 days later, the wight in control group was significantly loss( P <0. 01 ). Treatment with 50mg/kg/d M475271 not only reduced the mumber and the size of metastatic lesions, but also inhibited the number of Ki67 positive proliferating tumor cells in lung metastases produced by A549 cells( P <0. 001). Conclusion; Sre tyrosine kinase inhibition could suppress the pro-gression of lung metastasis by the inhibition of local cell proliferation and invasion of A549 cells.
[Key words]Sre tyrosine kinase; pulmonary metastasis tumor; proliferation index; microvessel density
Modern Oncology 2011,19(06) :1076 1079
【摘要】
目的：探讨抑制Sre酪氨酸激酶对小鼠肺转移瘤的干预作用及其机制。方法：采用雄性严重联合免
疫缺陷（SCID）小鼠，敲除NK细胞，建立肺腺癌A549细胞诱导的实验性肺转移癌动物模型。每天给予小鼠口服Src酪氨酸激酶抑制剂，研究抑制Sre酪氨酸激酶对实验性肺转移瘤的影响；采用免疫组化法研究抑制 Sre酪氨酸激酶对转移瘤中增生指数(Ki67染色）和微血管密度(CD31染色）的影响。结果：A549细胞在肺表面形成弥漫性的转移性损伤，50mg/kg/dSrc酪氮酸激酶抑制剂口服治疗组肺表面比对照组光滑，肺重量明显小于对照组和10mg/kg/d治疗组（P<0.05），面10mg/kg/d治疗组的肺重量和对照组相比没有明显差别。 0 氨酸激酶抑制剂50mg/kg/d，明显减少肺组织内转移性肺损伤的数目和面积，同时显著减少Ki67阳性的增生性肿瘤细胞数(P<0.001)。
结论：抑制Sre酪氨酸激酶通过抑制局部增殖和浸润抑制A549细胞诱导的肺转
移瘤。
【关键词]Sre酪氨酸激酶；肺转移瘤；增生指数；微血管密度
【中图分类号】R73-36
【文献标识码】A
【文章编号】16724992(2011)06107604
【收稿日期】【修回日期】【基金项目】
【作者单位】
2010 11 24
DOI:10. 3969/j. issn. 1672 4992. 2011. 06. 10
2011 01 25
辽宁省教育厅高等学校科研项目（编号；20061011）；辽宁省自然科学基金（编号：20082076）；辽宁省科技厅科学技术计刘项目
（编号：2010225028）
1中国医科大学附属盛京医院第二呼吸内科，辽宁
2中国医科大学附属盛京医院检验科，辽宁
沈阳
沈阳
110022
110004
沈阳
110001
3中国医科大学附属第一医院呼吸疾病研究所，辽宁
郑锐（1972-），男，辽宁沈阳人，博士，副教投，主要从事肺癌的基础与临床研究。E-mail；zhengr@sj-hospital.org
【作者简介】