岩藻糖氟化模拟类似物对乳腺癌细胞增殖、侵袭的影响及机制研究

目的研究岩藻糖的氟化模拟类似物2-氟-L-岩藻糖(2-fluoro-L-fucose,2FF)对乳腺癌MDA-MB231细胞增殖和侵袭的影响,并探讨其可能的作用机制。方法凝集素染色法检测2FF处理后乳腺癌细胞中核心岩藻糖的表达情况;CCK-8法测定2FF处理对乳腺癌细胞增殖能力的影响;Transwell实验法测定2FF处理后乳腺癌侵袭能力的变化;Western blotting分析Hippo信号通路相关蛋白的表达情况。结果 2FF可显著抑制乳腺癌MDA-MB231细胞中核心岩藻糖的表达,呈剂量和时间依赖性;2FF处理后可以显著抑制乳腺癌MDA-MB231细胞的增殖和侵袭;Westernblotting结果显示,2FF使用后,pYAP、pLATS、pMST1/2表达下降,总体YAP、LATS、MST1表达未见明显改变。结论 2FF可以抑制核心岩藻糖在乳腺癌细胞中的表达,并抑制乳腺癌细胞的增殖和迁移;其机制可能与Hippo信号通路的调节有关。

Effect and Mechanism of Fucose Fluoride Analogue Suppresses Breast Cancer Cell Proliferation and Migration

OBJECTIVE To investigate effect of fucose fluoride analogue(2-fluoro-L-fucose, 2FF) on the proliferation and invasion of breast cancer MDA-MB231 cells, and to explore the possible mechanism. METHODS Lectin blot was performed to detect the expression of core fucose in breast cancer cells after 2FF treatment. CCK-8 was used to determine the effect of 2FF treatment on the proliferation of breast cancer cells. The changes of invasive abilities of breast cancer cells after 2FF treatment were determined by Transwell assay and the expression of Hippo signaling pathway-related proteins were checked by Western blotting. RESULTS 2FF suppressed core fucosylation in the breast cancer, in a dose- and time-dependent manner. After treated by 2FF, the cell proliferation and migration was significantly inhibited. The expression of pYAP, pLATS, pMST1/2 was significantly decreased in the 2FF treated cells compared with the control cells. However, the expression of YAP, LATS, MST1 had little changes. CONCLUSION 2FF inhibit the expression of core fucosylation in the breast cancer cells, and inhibit the cell proliferation and migration. The mechanism may be related to the regulation of Hippo signaling pathway.