二氢杨梅素对4T1小鼠乳腺癌肺转移的抑制作用

Suppression of distant pulmonary metastasis of 4T1 mice breast carcinoma by dihydromyricetin administration

目的为了探讨二氢杨梅素的抗转移作用,在Balb/c雌性小鼠右后腿皮下建立了4T1乳腺癌移植模型,然后给予二氢杨梅素灌胃给药。方法 MTT法检测二氢杨梅素对4T1小鼠乳腺癌细胞的抗增殖作用;Transwell侵袭小室法检测二氢杨梅素对4T1细胞的抗转移作用。检测肿瘤的体积、远端肺转移灶数、荷瘤鼠血清及条件培养基中的基质金属蛋白酶MMP-9和MMP-2。结果二氢杨梅素处理4T1细胞48 h后,半数抑制浓度(IC50)为102.1μg/ml。二氢杨梅素能不依赖细胞毒作用减少细胞培养液中MMP-2和MMP-9水平,并且抑制4T1细胞的侵袭。与盐水对照组比较,100 mg·kg-1·d-1二氢杨梅素灌胃给药能显著减少瘤重、肺转移灶数以及荷瘤鼠血清MMP-9和MMP-2水平;而50 mg·kg-1·d-1二氢杨梅素灌胃给药组除了血清MMP-2水平外,没有显著差异。结论二氢杨梅素给药能抑制4T1小鼠乳腺癌远端肺转移,其机制可能与二氢杨梅素下调荷瘤小鼠血清MMP-9和MMP-2水平相关。

Objective To investigates anti-metastasis effect of DMY, 4T1 mice breast carcinoma xenograft models were established in right hind leg subcutaneous of female Balb/c mice followed by DMY administration intragastrically. Methods Anti-proliferation and anti-metastasis effect of DMY were determined by the MTT assay and Transwell model, respectively. Tumor volume, distant pulmonary metastatic loci, and matrix metalloproteinases（MMP-9/MMP-2） levels in tumor-bearing mice serums and the conditioned media were analyzed. Results After treated by DMY for 48 h, IC50 value was about 102.1 μg/ml. DMY decreased MMP-9/MMP-2 levels in media and inhibited the invasion of 4T1 cells without cytotoxicity against the cancer cells. Compared with saline control group, 100 mg·kg^-1·d^-1 DMY decreased significantly tumor weight, lung metastatic loci and serum MMP-9/MMP-2 levels, while 50 mg·kg^-1·d^-1 DMY showed no significant difference except serum MMP-2 level. Conclusion DMY administration could suppress distant pulmonary metastasis of 4T1 mice breast carcinoma, and the mechanism was positively correlated with the down-regulation of tumor-bearing mice serum MMP-9/MMP-2 level by DMY.