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目的观察右旋柠烯对人乳腺癌淋巴管生成和淋巴结转移的影响,探讨其抗肿瘤转移机制。方法24只裸鼠乳腺原位种植人乳腺癌细胞株MDA-MB-435,建立乳腺癌模型,分成模型对照组、右旋柠烯组和5-氟尿嘧啶(5-FU)组。检测肿瘤体积和腋窝淋巴结转移率,免疫组化法检测乳腺癌组织微淋巴管密度(LMVD)和血管内皮生长因子C(VEGF-C)。结果右旋柠烯组肿瘤体积(0·824±0·31)明显减小,腋窝淋巴结转移率(25·0%)明显减低,与模型对照组(2·178±0·35、87·5%)比较,差异有统计学意义(均P<0·01),与5-FU组(0·758±0·29、50%)比较,差异无统计学意义(均P>0·05);右旋柠烯组LMVD(13·80±5·91)明显降低,VEGF-C表达(3·54±0·68)下调,与模型对照组(28·59±7·21、5·40±0·89)和5-FU组(25·28±5·35、5·21±0·78)比较,差异有统计学意义(均P<0·01,均P<0·05)。结论右旋柠烯可能通过影响VEGF-C诱导的淋巴管生成抑制乳腺癌淋巴结转移。
Objective To observe the effect of d-limonene on lymphangiogenesis and lymph node metastasis in human breast cancer and to explore its antitumor metastasis mechanism. Methods Twenty-four nude mice were implanted with breast cancer cell line MDA-MB-435 in situ to establish a model of breast cancer. The model group was divided into model control group, D-limonene group and 5-fluorouracil group. Tumor volume and axillary lymph node metastasis were detected. Lymphatic vessel density (LMVD) and vascular endothelial growth factor C (VEGF-C) were detected by immunohistochemistry. Results The tumor volume (0.82 ± 0.31) and the axillary lymph node metastasis rate (25.0%) in D-limonene group were significantly lower than those in model control group (2.178 ± 0.35 and 87.5 %) (P <0.01). There was no significant difference between the 5-FU group and the 5-FU group (0.758 ± 0.29,50%) (all P> 0.05) (13 · 80 ± 5 · 91), and VEGF-C expression (3. 54 ± 0. 68) in D-limonene group were significantly lower than those in model control group (28.59 ± 7.21,5.40 ± 0.89) and 5-FU group (25.28 ± 5.35,5.221 ± 0.78), the difference was statistically significant (P <0.01, all P <0.05). Conclusion D-limonene may inhibit the lymph node metastasis of breast cancer by affecting the VEGF-C-induced lymphangiogenesis.