中药升清胶囊干预脂代谢异常对乳腺癌肝转移的影响

This subject designed to research on experimentally confirmed abnormal lipid metabolism may induce or accelerate breast cancer metastasis to the liver, and in Chinese medicine, "Shuganjianpi tongfu" theoretical guidance, explore effective drug treatment for breast cancer liver metastases Shengqing cupsules (Polygonum cuspidatum, rhubarb, orange peel). And from CXCL12-CXCR4 signaling pathway perspective, explore Shengqing cupsulesby regulating lipid metabolism and mechanism of action of inhibiting liver metastasis of breast cancer.After the high-fat diet model of liver metastasis of breast cancer cell lines to be vaccinated, the formation of abnormal lipid metabolism of breast cancer liver metastasis model, after the model is successful, each group was observed in vivo imaging of breast cancer metastases speed, surface and metastatic tumor size, drug intervention ended, mice in each group before and after the detection of drugs in blood free fatty acids, triglycerides, tumor weight and tumor weight inhibition rate of liver metastases count and liver metastasis inhibition rate, liver weight. RT-PCR, WestronBlot, immunohistochemical method to detect the primary tumor and liver tissue CXCL4, SDF-1, CXCR12, MPK expression. SQC confirmed by inhibiting CXCL12-CXCR4 signaling pathway, thereby inhibiting the mechanism of abnormal lipid metabolism induced breast cancer liver metastases.

本课题旨在通过实验研究，证实脂代谢异常可诱发或加速乳腺癌向肝脏转移，并在中医“疏肝健脾通腑”理论指导下，发掘治疗脂代谢异常诱发乳腺癌肝转移的有效药物升清胶囊（虎杖、大黄、陈皮）。并从CXCL12-CXCR4信号通路角度出发，探讨升清胶囊通过调节脂代谢而抑制乳腺癌肝转移的作用机制。高脂饮食模型建立后予乳腺癌肝转移细胞株接种，形成脂代谢异常乳腺癌肝转移模型，造模成功后，活体成像观察各组发生乳腺癌肝转移的速度、体表及转移瘤大小，药物干预结束，检测用药前后各组裸鼠血液中游离脂肪酸、甘油三酯含量、瘤重及瘤重抑制率、肝转移灶计数及肝转移抑制率、肝重。RT-PCR、WestronBlot、免疫组化法检测原发灶及肝组织中CXCL4，SDF-1，CXCR12， MPK的表达。证实升清胶囊能通过抑制CXCL12-CXCR4信号通路，从而抑制脂代谢异常所诱发的乳腺癌肝转移的作用机理。

本课题旨在通过实验研究，证实脂代谢异常可诱发或加速乳腺癌向肝脏转移，并在中医“疏肝健脾通腑”理论指导下，发掘治疗脂代谢异常诱发乳腺癌肝转移的有效药物升清胶囊（虎杖、大黄、陈皮）。并从CXCL12-CXCR4信号通路角度出发，探讨升清胶囊通过调节脂代谢而抑制乳腺癌肝转移的作用机制。高脂饮食模型建立后予乳腺癌肝转移细胞株接种，形成脂代谢异常乳腺癌肝转移模型，造模成功后，活体成像观察各组发生乳腺癌肝转移的速度、体表及转移瘤大小，药物干预结束，检测用药前后各组裸鼠血液中游离脂肪酸、甘油三酯含量、瘤重及瘤重抑制率、肝转移灶计数及肝转移抑制率、肝重。RT-PCR、Western Blot、免疫组化法检测原发灶及肝组织中CXCL4，SDF-1，CXCR12， MPK的表达。证实升清胶囊能通过抑制CXCL12-CXCR4信号通路，从而抑制脂代谢异常所诱发的乳腺癌肝转移的作用机理。.本课题在体外细胞检测了升清胶囊同样配方中药大鼠灌胃后获取的药物血清在体外，对于MDA-MB-231细胞增值、迁移、侵袭活性的影响；在体内水平，验证了升清胶囊对裸鼠脂肪代谢以及MDA-MB-231原位移植瘤肝转移的影响。