Proliferation of human lung cancer in an orthotopic transplantation mouse model

Proliferation of human lung cancer in an orthotopic transplantation mouse model
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DOI:
10.3892/etm_00000073
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发表时间:
2010-05-01
影响因子:
2.7
通讯作者:
Inoue, Tomio
Inoue, Tomio
中科院分区:
医学4区
文献类型:
--
作者:
Kang, Yun;Omura, Motoko;Inoue, Tomio

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本研究的目的是阐明人肺癌原位移植模型中的生长和增殖方式。使用人肺鳞状细胞癌SQ5和腺癌A549细胞系。将悬浮在无血清培养基中的肿瘤细胞直接注射到麻醉的雌性Balb/c无胸腺裸鼠的主支气管中,同时给予0.01 M乙二胺四乙酸。在处死前20分钟将溴脱氧尿苷注射到小鼠中。将具有肿瘤结节和皮下肿瘤的肺组织固定并通过组织学检查确认。计数肿瘤区溴脱氧尿苷标记细胞,计算增殖指数。在SQ5-和A549-细胞原位移植的小鼠中获得不同大小的肺肿瘤集落。原位SQ5肿瘤小直径40-700 μ m,大直径80-830 μ m,无明显坏死。原位SQ5肿瘤的小直径为540- 5200 μ m,大直径为600- 6100 μ m,肿瘤中心有明确的坏死。在原位A549肿瘤中也发现了类似的结果。有/无坏死的原位SQ5肿瘤的增殖指数分别为7.38(3.03)/10.63(3.10),有坏死的皮下SQ5肿瘤的增殖指数分别为6.99(2.10)。有/无坏死的原位A549肿瘤的增殖指数分别为2.70(0.88)、13.53(1.70),有坏死的皮下A549肿瘤的增殖指数分别为3.91(0.63)。本研究结果提示,该原位移植模型可为肺癌的生长提供适宜的器官微环境,并可能适用于人肺癌的靶向治疗研究。
The objective of this study was to clarify the growth and proliferation style of human lung cancer grown in an orthotopic transplantation model. The human lung squamous cell carcinoma SQ5 and adenocarcinoma A549 cell lines were used. Tumor cells suspended in serum-free medium were directly injected into the main bronchi of anesthetized female Balb/c athymic nude mice with simultaneous administration of 0.01 M ethylenediaminetetraacetic acid. Bromodeoxyuridine was injected into mice 20 min before sacrifice. Lung tissue with tumor nodules and subcutaneous tumors were fixed and confirmed by histological examinations. Bromodeoxyuridine-labeled cells in the tumor area were counted, and the proliferation index was calculated. Lung tumor colonies of various sizes were obtained in the SQ5- and A549-cell orthotopically transplanted mice. Orthotopic SQ5 tumors whose minor diameter was 40-700 mu m and major diameter was 80-830 mu m showed no definite necrosis. Orthotopic SQ5 tumors whose minor diameter was 540-5,200 mu m and major diameter was 600-6,100 mu m showed definite necrosis in the tumor center. Similar results were also found in the orthotopic A549 tumors. The proliferation index was 7.38 (3.03)/10.63 (3.10) in the orthotopic SQ5 tumors with/without necrosis and 6.99 (2.10) in the subcutaneous SQ5 tumors with necrosis, respectively. The proliferation index was 2.70 (0.88)13.53 (1.70) in the orthotopic A549 tumors with/without necrosis and 3.91 (0.63) in the subcutaneous A549 tumors with necrosis, respectively. The data suggest that this orthotopic transplantation model may provide the proper organ microenvironment for lung cancer growth and may be suitable for the target therapy research of human lung cancer.