| 陆相前 肖文静 沈方臻 孙同琳 李晓 姚如永.Celecoxib抑制Lewis 肺癌移植瘤淋巴管生成的作用机制及量效关系[J].现代生物医学进展英文版,2014,14(33):6425-6431. |
| Celecoxib抑制Lewis 肺癌移植瘤淋巴管生成的作用机制及量效关系 |
| The Inhibitory Effect of Celecoxib on Lewis Lung TumorLymphangiogenesis and Dose-response Relationship |
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| DOI： |
| 中文关键词: Lewis肺癌 塞来昔布 环氧化酶-2 微淋巴管密度 免疫组织化学 |
| 英文关键词: Lewis Lung Carcinoma Celecoxib Cyclooxygenase-2 LMVD Immunohistochemical |
| 基金项目:国家自然科学基金项目（30872169） |
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| 中文摘要: |
| 目的：COX-2 过度表达及淋巴管的生成与肺癌早期转移、不良预后密切相关。观察不同剂量COX-2 特异性抑制剂Celecoxib
对Lewis 肺癌移植瘤生长、COX-2、VEGF-C 表达和微淋巴管生成影响，探讨Celecoxib 对Lewis 肺癌移植瘤淋巴管生成可能作用
机制及量效关系。方法：将Lewis 肺癌细胞株接种于C57BL/6 小鼠左侧腹股沟皮下建立移植瘤模型，随机分为4 组：对照组、塞来
昔布低剂量(30 mg·kg-1·d-1)、中剂量(90 mg·kg-1·d-1)、高剂量(180 mg·kg-1·d-1)组。观察荷瘤小鼠生存状态，瘤体积变化，计算抑瘤
率，种瘤42 天后牺牲小鼠，切取移植瘤组织，免疫组化染色检测COX-2、VEGF-C 表达及微淋巴管密度（Lymphatic microvessel
density，LMVD）。结果：塞来昔布低、中、高剂量组的抑瘤率分别为13.3%、46.8%和56.3%。塞来昔布高、中剂量组较对照组抑瘤作
用明显，差异有统计学意义(P＜0.05)，但低剂量组差异无统计学意义（P＞0.05）。免疫组织化学染色结果分析显示：塞来昔布高、中
剂量组COX-2、VEGF-C 的表达水平及微淋巴管密度均明显减低，差异有统计学意义(P＜0.05)，低剂量组略有减低但差异无统计
学意义（P＞0.05）。抑制程度呈明显的剂量依赖性。结论：塞来昔布抑制Lewis肺癌移植瘤的生长及淋巴转移，可能与下调COX-2
的表达，减少VEGF-C 的产生，抑制微淋巴管生成有关，该抑制作用呈一定的剂量相关性，为抗肺癌早期淋巴转移，改善患者预后
的药物研发提供了一定的实验基础。 |
| 英文摘要: |
| Objective:COX-2 overexpression and lymphangiogenesis have been related to early-metastasis and poor prognosis in
lung cancer. To observe the effect of different doses of Celecoxib, a cyclooxygenase-2 inhibitor, on tumor growth, COX-2, VEGF-C
expression and lymphangiogenesis in Lewi Lung Carcinoma homograft in C57BL/6 mice and explore the possible role of Celecoxib on
Lewis lung tumor lymphangiogenesis mechanism and the dose-response relationship.Methods:Lewi Lung Carcinoma cell lines were
seeded in C57BL / 6 left groin subcutaneous to establish homograft models. These models were randomly divided into four groups:
control group , low-dose（30 mg·kg-1·d-1) group, medium-dose (90 mg·kg-1·d-1) group , and high dose (180 mg·kg-1·d-1) group. Then we
observed the tumor-bearing survival statuses and tumor volume changes of the mice. Transplanted tumor tissues were collected after 42
days and we made a detection of COX-2, VEGF-C expression and lymphatic microvessel density by immunohistochemical staining
method.Results:Low-dose group, medium-dose group and high-dose group of Celecoxib inhibition rates were 13.3%, 46.8%and 56.3%,
respectively. Compared with the control group. There were significant statistacally differences in the inhibitory effect on tumors of high
and medium-dose groups (P<0.05), however, no difference could be seen in low-dose group (P>0.05). Immunohistochemical staining
showed that celecoxib with medium and high-dose lowered the expressions of COX-2, VEGF-C and lymphatic microvessel density
（LMVD）. And compared with the control group, there were significant differences (P<0.05). Though expressive levels decreased
slightly, there were no significant differences between Low-dose group and control group (P>0.05). The degree of inhibition was
dose-related.Conclusion:Celecoxib inhibits the growth of Lewis lung tumor and lymph node metastasis by reducing expressions of
COX-2 and VEGF-C and inhibiting lymphangiogenesis which is related to dosage. That provides certain experimental basis for drug
development of anti-cancer lymph node metastasis in early stage and the patients prognosis improvement. |
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