1. 上海中医药大学附属龙华医院浦东分院普外科,上海,200126
2. 上海中医药大学附属龙华医院中西医结合乳腺科,上海,200032
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宋晓耘, 王玉, 张帅, 等. 升清胶囊干预脂代谢异常对乳腺癌肝转移的影响[J]. 上海中医药杂志, 2017,51(7):85-90.
SONG Xiao-yun, WANG Yu, ZHANG Shuai, et al. Effects of Shengqing Capsule on abnormal lipid metabolism and breast cancer with liver metastasis[J]. Shanghai Journal of Traditional Chinese Medicine, 2017,51(7):85-90.
目的:探讨中药升清胶囊通过干预CXCL12-CXCR4信号通路对脂代谢异常的调节及其对乳腺癌肝转移的影响。 方法:①选用人乳腺癌细胞株MDA-MB-231,分为对照组(Con)、空白血清组(Black)、表阿霉素组(Epirubicin)以及升清胶囊血清低浓度组(SQ-L)、高浓度组(SQ-H)。采用MTT法检测药物血清对细胞增殖的影响,并用划痕愈合实验和Transwell实验检测其对细胞迁移及侵袭能力的影响。同时采用Western blotting法检测CXC趋化因子配体12(CXCL12)与其特异性受体CXCR4以及蛋白激酶B(AKT),磷酸化蛋白激酶B(p-AKT),B淋巴白血病淋巴瘤-2基因(Bcl-2),基质金属蛋白酶9(MMP-9)蛋白表达水平的变化。②建立脂代谢异常乳腺癌肝转移动物裸鼠模型,用升清胶囊0.25 g·kg-1,或表阿霉素5 μg·g-1干预治疗,检测血浆游离脂肪酸(FFA)、三酰甘油(TG)水平变化及对乳腺癌肝转移的影响。 结果:①MTT结果表明,升清胶囊和表阿霉素药物血清干预后,MDA-MB-231细胞存活率显著降低,且呈浓度依赖性持续降低(P<0.05)。Transwell和划痕愈合实验结果表明,升清胶囊药物血清能够显著抑制细胞的侵袭和迁移能力。Western blotting结果表明,与对照组比较,升清胶囊药物可降低趋化因子CXCL12以及受体CXCR4蛋白表达水平(P<0.05),同时下调MMP-9和Bcl-2蛋白表达,且p-AKT水平降低(P<0.05)。②动物实验表明,升清胶囊可以显著降低脂代谢异常裸鼠TG、FFA水平(P<0.05),抑制乳腺癌肝转移。 结论:升清胶囊能够通过抑制趋化因子CXCL12-CXCR4和相关信号通路活性,下调血脂水平,抑制乳腺癌转移。
Objective:To discuss the effects of Shengqing Capsule on abnormal lipid metabolism and breast cancer with liver metastasis by CXCL12-CXCR4 signaling pathway. Methods(1) Human breast cancer cells line MDA-MB-231 was selected and divided into the control group, blank serum group, Epirubicin group and Shengqing Capsule groups with high-and low-concentration. Each group was treated with the corresponding drug contained serum. The effect of drug contained serum on cell proliferation was detected by MTT assay,the effects of drug contained serum on cell migration and invasion were detected by scratch test and Transwell assay. The protein expressions of chemokine ligand CXCL12 and its specific receptor CXCR4 and phosphorylated protein kinase B(p-AKT), protein kinase B(AKT), B-cell leukemia lymphoma-2(Bcl-2)and matrix metallopeptidase-9(MMP-9)were detected by Western blotting. (2) Nude mouse model of breast cancer with liver metastasis and abnormal lipid metabolism was established. The Shengqing Capsule at dose of 0.25 g·kg-1 and Epirubicin at dose of 5 μg·g-1 were given for intervention. The level changes of free fatty acid (FFA) and triglyceride (TG) in plasma were detected,and the effects of Shengqing Capsule on breast cancer with liver metastasis were evaluated. Results:(1) The MTT assay showed that drug contained serum of Shengqing Capsule and Epirubicin could significantly decrease the survival rate of MDA-MB-231 cells in a concentration-dependent manner(P<0.05). The scratch test and Transwell assay showed that drug contained serum of Shengqing Capsule could significantly inhibit the cell invasion and migration. The results of Western blotting showed that drug contained serum of Shengqing Capsule could decrease the protein expressions of CXCL12 and CXCR4 compared with the control group(P<0.05),and down-regulate the protein expressions of MMP-9 and Bcl-2 and reduce the p-AKT level(P<0.05).(2)The results of animal experiment showed that Shengqing Capsule could significantly decrease the levels of TG and FFA in nude mice with abnormal lipid metabolism(P<0.05),and inhibit the liver metastasis of breast cancer. Conclusion:Shengqing Capsule can down-regulate the blood lipid levels and suppress the liver metastasis of breast cancer by inhibiting the expressions of CXCL12,CXCR4 and the related signaling pathway.
升清胶囊乳腺癌肝转移人乳腺癌细胞株MDA-MB-231CXC趋化因子配体12CXCR4
shengqing Capsulebreast cancer with liver metastasishuman breast cancer cells line MDA-MB-231CXCL12CXCR4
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