VEGF-C反义寡核苷酸对人乳腺癌淋巴转移的影响

Effect of VEGF-C antisense oligodeoxyribonucleotide on lymphatic metastasis of human breast cancer

关键词:  乳腺癌  血管内皮生长因子C  反义寡核苷酸  淋巴转移

Key words:  breast cancer  vascular endothelial growth factorC  antisense oligonucleotide  lymphatic metastasis

摘要:

［目的］ 研究血管内皮生长因子C（VEGF-C）反义寡核苷酸（ASODN）对人乳腺癌淋巴管形成及淋巴结转移的影响。［方法］ 人乳癌细胞MDA-MB-435裸小鼠乳腺脂肪垫接种建立乳癌转移模型，接种后3 d，随机分组，对照组、顺义寡核苷酸组（SODN）和ASODN组，每组8只。在肿瘤细胞接种局部分别注射给药，检查肿瘤转移情况，免疫组织化学法检测肿瘤VEGF-C表达和淋巴管密度（LMVD）。［结果］ 对照组、SODN组和ASODN组肿瘤体积分别为：(2.178±0.35)cm³、(2.304±0.29)cm³和(0.324±0.11)cm³；腋窝淋巴结转移率为：87.5％、75.0％和25.0％；其它脏器转移率为：75.0％75.0％和25.0％；VEGF-C蛋白表达评分分别为：5.40±0.89、5.30±0.98和3.38±0.88；LMVD分别为：28.59±7.21、26.28±5.35和15.80±5.91。ASODN组各项指标与对照组和SODN组比较均有显著差异（P<0.05）。相关分析表明，VEGF-C表达与LMVD和肿瘤淋巴结转移显著相关。［结论］ VEGF-C反义寡核苷酸通过抑制淋巴管形成而抑制乳癌淋巴结转移，可以作为乳癌治疗的一种辅助手段。

Abstract:

［Objective］ To investigate the effect of vascular endothelial growth factor C (VEGF-C) on the lymphangiogenesis and lymphatic metastasis of human breast cancer. ［Methods］ The subcultured human breast cancer cell MDA-MB-435 were orthotopicaly implanted into the mammary fat pad of female nude mice to establish a metastatic breast cancer model. Three daysafter implantation, mice were divided into 3 groups: the control group, the sense oligonucleotide (SODN) group and with the antisense oligonucleotide (ASODN) group. VEGF-C oligonucleotide or and injected locally with was. In the 9th week, mice were sacrificed, the sizes of tumors were measured and the inhibition rates were calculated, the metastatic condition was examined. Immunohistochemistry (IHC) method was used to detect the VEGF-C expression and the lymphatic microvessel density (LMVD). ［Results］ In the control group, SODN group and ASODN group, the tumor volume were (2.178±0.35)cm3,(2.304±0.29)cm3 and (0.324±0.11)cm3 respectively; the metastatic rate to axillary lymph node were 87.5%, 75.0%and 25.0% respectively ; the metastatic rate to other organs were 75.0%、75.0% and 25.0%; the VEGF-C expression level were 5.40±0.89, 5.30±0.98, 3.38±0.88 and the LMVD were 28.59±7.21、26.28±5.35 and 15.80±5.91 respectively . All the results of the parameters detected above showed a significant difference between the ASODN group and other two growps (Ｐ<0.05). The correlation analysis suggested a close relationship of VEGF-C expression to LMVD and lymph node metastasis. ［Conclusions］ VEGF-C antisense oligonucleotide may inhibit the lymph node metastasis of breast cancer by the suppression of lymphangiogenesis induced by VEGF-C expression. VEGF-C antisense oligonucleotide can be used as a new therapy for breast cancer.