【摘要】：研究目的：觀察內(nèi)皮抑素對(duì)人舌鱗癌腫瘤的生長(zhǎng)、脈管生成及頸淋巴轉(zhuǎn)移的影響,并對(duì)內(nèi)皮抑素抑制脈管生成可能的機(jī)制進(jìn)行分析。 研究方法：本研究應(yīng)用Tca83舌鱗癌細(xì)胞系建立裸鼠舌癌原位移植模型,將裸鼠隨機(jī)分為A、B、C共3組,分別給予A組皮下注射生理鹽水0.1ml；B組皮下注射內(nèi)皮抑素10mg/kg/d；C組皮下注射內(nèi)皮抑素20mg/kg/d。每日注射藥物一次,連續(xù)給予兩周。觀察舌癌動(dòng)物模型腫瘤生長(zhǎng)及淋巴轉(zhuǎn)移特點(diǎn),采用免疫組織化學(xué)方法標(biāo)記病灶中的脈管。并檢測(cè)VEGF-C的表達(dá)情況,計(jì)數(shù)病灶脈管密度及VEGF-C陽性率。采用SPSS20.0軟件包對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果：1、實(shí)驗(yàn)組裸鼠較對(duì)照組腫瘤生長(zhǎng)減慢,實(shí)驗(yàn)結(jié)束時(shí)腫瘤體積A組為5.838±0.095mm3,B組為3.554±0.061mm3,C組為2.578±0.074mm3。內(nèi)皮抑素對(duì)腫瘤生長(zhǎng)具有抑制作用。進(jìn)一步計(jì)算各組標(biāo)本微血管密度,A組為10.4±1.26個(gè)/視野,B組為4.4±0.84個(gè)/視野,C組為2.2±0.79個(gè)/視野。內(nèi)皮抑素對(duì)腫瘤血管生成具有抑制作用,且隨劑量增加,抑制作用增強(qiáng)。 2、高劑量組裸鼠較對(duì)照組和低劑量組淋巴轉(zhuǎn)移率低,A組為50%,B組為20%,C組為0%。高劑量?jī)?nèi)皮抑素對(duì)腫瘤淋巴轉(zhuǎn)移具有抑制作用。進(jìn)一步計(jì)算各組標(biāo)本微淋巴管密度,A組為6.2±0.92個(gè)/視野,B組為4.0±1.05個(gè)/視野,C組為2.2±0.92個(gè)/視野。內(nèi)皮抑素對(duì)腫瘤淋巴管生成具有抑制作用,且隨劑量增加,抑制作用增強(qiáng)。 3、另外,A組VEGF-C陽性率為80%；B組VEGF-C陽性率為40%；C組VEGF-C陽性率為20%。高劑量?jī)?nèi)皮抑素可以下調(diào)腫瘤細(xì)胞VEGF-C的表達(dá)。 結(jié)論：1、腫瘤血管生成在腫瘤生長(zhǎng)中發(fā)揮重要作用,內(nèi)皮抑素可以抑制腫瘤血管生成,從而抑制腫瘤生長(zhǎng),且具有劑量依賴性,隨濃度增加其抑制作用逐漸增強(qiáng),但未見其縮小抑或消除腫瘤的作用。 2、腫瘤淋巴管生成在惡性腫瘤的侵襲轉(zhuǎn)移過程中具有重要作用,高劑量?jī)?nèi)皮抑素可以抑制腫瘤淋巴管生成,從而抑制腫瘤淋巴轉(zhuǎn)移。 3、內(nèi)皮抑素可能是通過下調(diào)細(xì)胞VEGF-C的表達(dá)進(jìn)而抑制腫瘤淋巴管生成。
[Abstract]:Aim: to observe the effects of endostatin on the growth, angiogenesis and cervical lymphatic metastasis of human tongue squamous cell carcinoma, and to analyze the possible mechanism of endostatin inhibiting angiogenesis. Methods: in this study, Tca83 tongue squamous cell carcinoma cell line was used to establish orthotopic transplantation model of tongue carcinoma in nude mice. Nude mice were randomly divided into 3 groups: group A was subcutaneously injected with normal saline 0.1 ml. Group B was subcutaneously injected with endostatin 10 mg / kg / d and group C was subcutaneously injected with 20 mg / kg / d endostatin. The drug was injected once a day for two weeks. To observe the characteristics of tumor growth and lymphatic metastasis in tongue cancer animal model and to label the vessels in the lesion by immunohistochemical method. The expression of VEGF-C, vascular density and positive rate of VEGF-C were measured. The data were analyzed by SPSS20.0 software package. Results: 1. The tumor growth of the nude mice in the experimental group was slower than that in the control group. At the end of the experiment, the tumor volume of group A was 5.838 鹵0.095 mm ~ (3) and that of group B was 3.554 鹵0.061 mm ~ (3) and that of group C was 2.578 鹵0.074 mm ~ (3). Endostatin inhibits tumor growth. The microvessel density of group A was 10.4 鹵1.26 / visual field, group B was 4.4 鹵0.84 / visual field, group C was 2.2 鹵0.79 / visual field. Endostatin has inhibitory effect on tumor angiogenesis, and the inhibitory effect is enhanced with the increase of dose. 2, the lymphatic metastasis rate of the nude mice in the high dose group was lower than that in the control group and the low dose group, and the lymph node metastasis rate in group A was 50 and that in group B was 20. High dose endostatin can inhibit lymphatic metastasis of tumor. The density of microlymphatic vessels in each group was 6.2 鹵0.92 / visual field, 4.0 鹵1.05 / visual field in group B and 2.2 鹵0.92 / visual field in group C. Endostatin has inhibitory effect on lymphangiogenesis of tumor, and the inhibitory effect is enhanced with the increase of dose. In addition, the positive rate of VEGF-C in group A was 80 and the positive rate of VEGF-C in group B was 40. The positive rate of VEGF-C in group C was 20. High dose endostatin can down-regulate the expression of VEGF-C in tumor cells. Conclusion: 1. Tumor angiogenesis plays an important role in tumor growth. Endostatin can inhibit tumor angiogenesis and inhibit tumor growth in a dose-dependent manner. However, it has not been seen to shrink or eliminate the role of tumor. 2. Tumor lymphangiogenesis plays an important role in the invasion and metastasis of malignant tumor. High dose of endostatin can inhibit lymphangiogenesis of tumor and thus inhibit lymphatic metastasis of tumor. 3. Endostatin may inhibit lymphangiogenesis by down-regulating the expression of VEGF-C.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.86

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