附子-白术“药对”干预乳腺癌骨转移骨质流失的作用机制

Bone loss is the current difficulties in the treatment of bone metastases of breast cancer.Bone protection becomes a key link in its treatment.It was found that spleen kidney yang deficiency syndrome of breast cancer patients with bone metastases was more common in clinical practice. The pair of Baizhu and Fuzi hit the TCM pathogenesis.Our preliminary experiments found the pair of Baizhu and Fuzi for the prevention and treatment of breast cancer bone metastasis, but its mechanism of action remains to be further explored.To this end, we propose the hypothesis: spleen and kidney yang deficiency is the main pathogenesis of bone metastases in breast cancer; The pair of Baizhu and Fuzi macrocephala played the role of rescuing bone loss and repairing injuries to the residual bone by means of regulation of TGF β-Smads-Gli2-PTHrP signaling pathway; Baizhu played a role to enhancements of the Fuzi efficacy of compatibility. To verify this hypothesis, we will use the breast cancer bone metastasis nude mouse model,breast cancer cells, osteoclasts, osteoblasts, osteoclasts and osteoblasts co-culture model to study and research above-mentioned questions from genes, proteins, cells, tissue and whole animal by using RT-PCR, Western blot, immunohistochemistry, LC-MS/MS.The subject will clarify bone metastasis of breast cancer of spleen and kidney yang deficiency scientificly from a new visual.which will provide a new way of prevention and treatment andTraditional Chinese Medicine Pathogenesis and research mentality of the breast cancer bone metastasis.

骨质流失是目前乳腺癌骨转移治疗中的难点，骨保护成为其治疗的关键环节。临床实践发现乳腺癌骨转移患者脾肾阳虚证多见，附子-白术药对切中该病机。我们的预实验发现附子-白术药对可用于防治乳腺癌骨转移，但其作用机制还有待进一步探讨。为此，我们提出假说：脾肾阳虚为乳腺癌骨转移的主要病机；附子-白术药对通过调控TGFβ-Smads-Gli2-PTHrP信号通路，而起到挽救骨质流失、修复残骨损伤的作用；白术在该药对配伍中主要起到增强附子疗效的作用。为验证该假说，我们将通过乳腺癌骨转移裸鼠模型、乳腺癌细胞、破骨细胞、成骨细胞、破骨细胞和成骨细胞共培养体系，采用RT-PCR、Western blot、免疫组化、LC-MS/MS等手段，从基因、蛋白、细胞、组织及整体动物等多层次研究上述问题。本课题将从新的视角阐明乳腺癌骨转移“脾肾阳虚”病机的科学性，为乳腺癌骨转移的中医药防治提供新的病机认识和研究思路。