VEGF-A/VEGF-C反义脱氧寡核苷酸对乳腺癌生长及其脉管生成的影响  

Effects of VEGF-A/VEGF-C Antisense Oligodeoxynucleotide on Angiogenesis, Lymphangiogenesis, and Tumor Growth of Breast Cancer

作　　者：陈基善[1] 张雅洁[1] 胡帅尔[2] 张惠球[1] 

机构地区：[1]广州医学院病理学教研室 [2]广东省疾病预防控制中心,广东广州510300

出　　处：《癌症》2007年第9期972-976,共5页Chinese Journal of Cancer

基　　金：广东省科技厅科技计划项目(No.2004B30601011);广州市科技局技术项目(No.2006J1-C0151);广州市属高校科技;社科项目(No.61002)~~

摘　　要：背景与目的:肿瘤脉管生成与肿瘤的生长和转移密切相关,血管内皮生长因子A(vascular endothelial growth factor-A,VEGF-A)可能是最强的促血管生成因子,而VEGF-C是VEGF家族中最强的促淋巴管生成因子,在肿瘤血管生成中与VEGF-A具有协同促进效应。本研究旨在探讨VEGF-A/VEGF-C反义脱氧寡核苷酸(antisense oligodeoxynucleotide,ASODN)对乳腺癌生长及其脉管生成的影响。方法:将VEGF-A/VEGF-CASODN注入人乳腺癌裸鼠原位移植瘤模型中,观察肿瘤生长;运用RT-PCR法检测肿瘤组织VEGF-A/VEGF-CmRNA表达,免疫组织化学法检测其蛋白表达情况;5′-Nase-ALPase双重酶组织化学染色标记肿瘤微血管和微淋巴管,并计算肿瘤微血管密度(microvessel density,MVD)和微淋巴管密度(lymphatic microvessel density,LMVD)。结果:反义组成瘤时间较对照组长[(13.00±2.83)天vs.(7.67±1.63)天,P<0.05],移植瘤生长速度较对照组缓慢,肿瘤重量明显低于对照组[(0.45±0.14)gvs.(0.92±0.37)g,P<0.05],抑瘤率达51.09%;反义组VEGF-A和VEGF-CmRNA及蛋白表达较对照组明显减弱(P<0.05),且MVD(21.83±2.86vs.41.33±4.03)及LMVD(18.67±4.67vs.31.83±2.33)显著低于对照组(P<0.05)。结论:VEGF-A/VEGF-CASODN通过抑制VEGF-A及VEGF-C表达抑制乳腺癌脉管生成,进而抑制肿瘤生长。BACKGROUND ＆ OBJECTIVE： Angiogenesis and lymphangiogenesis are closely related to tumor metastasis. Vascular endothelial growth factor-A （VEGF-A） is considered as an important factor in promoting angiogenesis; while VEGF-C is the most critical factor in VEGF family in promoting lymphangiogenesis, and exerts synergistic effect with VEGF-A in angiogenesis. This study was to investigate the effects of VEGF-A/VEGF-C antisense oligodeoxynucleotide （ ASODN） on the angiogenesis, lymphangiogenesis, and tumor growth of breast cancer. METHODS： VEGF-A/VEGF-C ASODN was constructed and injected into orthotopic transplantation tumor model of human breast cancer in athymic mice. Tumor growth was observed. The expression of VEGF-A and VEGF-C was detected by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry. Microvessel density （MVD） and lymphatic microvessel density （LMVD） were measured by enzymohistochemistry. RESULTS： Tumor formation time was significantly longer and tumor weight was significantly lower in ASODN group than in control group [ （13.00±2.83） days vs. （7.67±1.63） days, P〈0.05; （0.45±0.14） g vs. （0.92±0.37） g, P〈 0.05]. The inhibition rate of tumor growth was 51.09% in ASODN group. The mRNA and protein expression of VEGF-A and VEGF-C were significantly weaker in ASODN group than in control group （P〈0.05） The MVD and LMVD was significantly lower in ASODN group than in control group （21.83±2.86 vs. 41.33±4.03, 18.67±4.67 vs. 31.83±2.33, P〈0.05）. CONCLUSION： VEGF-A/VEGF-C ASODN could inhibit angiogenesis and lymphangiogenesis in breast cancer, and further inhibit tumor growth and metastasis.

关 键 词：反义脱氧寡核苷酸 VEGF—A VEGF—C 血管生成 淋巴管生成 乳腺肿瘤 

分 类 号：R737.9[医药卫生—肿瘤]