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[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。
[Objective] To investigate the effect of vascular endothelial growth factor C (VEGF-C) antisense oligonucleotide (ASODN) on lymphangiogenesis and lymph node metastasis in human breast cancer. [Methods] Breast cancer metastasis model was established by inoculation of mammary fat pad of human breast cancer cell line MDA-MB-435. Three days after inoculation, the mice were randomly divided into control group, cisplatin group (SODN) and ASODN group only. Tumor cell inoculation were injected separately locally, the tumor metastasis was examined, and the expression of VEGF-C and lymphatic vessel density (LMVD) were detected by immunohistochemistry. [Results] The tumor volume of the control group, SODN group and ASODN group were (2.178 ± 0.35) cm3, (2.304 ± 0.29) cm3 and (0.324 ± 0.11) cm3 respectively. The rates of axillary lymph node metastasis were 87.5%, 75.0% and 25.0 %. The rates of other organs were 75.0%, 75.0% and 25.0%, respectively. The scores of VEGF-C protein expression were 5.40 ± 0.89, 5.30 ± 0.98 and 3.38 ± 0.88, respectively. The LMVD were 28.59 ± 7.21,26.28 ± 5.35 And 15.80 ± 5.91. The indexes of ASODN group were significantly different from those of control group and SODN group (P <0.05). Correlation analysis showed that VEGF-C expression was significantly associated with LMVD and tumor lymph node metastasis. [Conclusion] VEGF-C antisense oligonucleotide can inhibit breast cancer lymph node metastasis by inhibiting lymphangiogenesis, which can be used as an adjunct to breast cancer therapy.