基于miRNA调节Wnt/β-catenin通路的鸡血藤抗乳腺癌转移的分子机制研究

It is universally acknowledged that tumor micro-environment demonstrates a significant effect on the metastasis of breast cancer, which is a promising area in the treatment of breast cancer. Based on our previous study , Suberect Spatholobus (SS) could inhibit breast cancer cell proliferation as well as angiogenesis, balance hypoxia，acidification in tumor environment and inhibit invasion and metastasis of breast cancer. In the recent study conducted by us, it suggested that SS could have a vital role to play in reversing epithelia - mesenchyme transition (EMT), the important process of tumor migration, by improving tumor microenvironment. Using microarray miRNA, we found that SS may significantly upregulate the expression of miR-200b and miR-200c, and downregulate the expression of miR-374a in the breast cancer cells. The studies indicated that miR-374a could activate Wnt / β-catenin pathway to promote the formation of EMT in breast cancer. Preliminary experiments predict Wnt1 was found to be common target genes for miR-200b and miR-200c. The hypothesis of this project is SS can improve the tumor microenvironment through down regulating miR-374a and upregulating miR-200b /c, and commonly reverse EMT by regulating Wnt / β-catenin pathway, which is the mechanism of the inhibitory effect on invasion and metastasis of breast cancer. This project will adopt the qRT-PCR, Western blot, in vivo animal imaging techniques to explore the molecular mechanisms of the inhibitory effect of SS on invasion and metastasis of breast cancer, and provide an experimental basis for the development of breast cancer and targeted therapy.

肿瘤微环境与转移是目前研究的重点与热点。申请者已证实鸡血藤(SS)可抑制乳腺癌增殖及血管生成，纠正肿瘤微环境的缺氧及酸化，也发现SS抑制乳腺癌侵袭与转移，逆转上皮-间质转化（EMT）。通过miRNA芯片验证发现SS显著上调乳腺癌细胞miR-200b/c的表达，下调miR-374a的表达。在乳腺癌中miR-374a可激活Wnt/β-catenin 通路促进EMT形成。预实验显示Wnt1是miR-200b/c共同靶基因。综上提出科学假说：SS可改善肿瘤微环境(包括EMT)，下调miR-374a，上调miR-200b/c共同阻断Wnt/β-catenin，进而实现抑制乳腺癌转移。本项目采用qRT-PCR、Western blot、体内动物成像等技术从miRNA、肿瘤微环境(EMT)等探讨SS抗乳腺癌侵袭转移的分子机制，为活血养血中药SS防治乳腺癌转移提供理论和实验依据。

肿瘤微环境与转移是目前研究的重点与热点。申请者已证实鸡血藤(SS)可抑制乳腺癌 增殖及血管生成，纠正肿瘤微环境的缺氧及酸化，也发现SS抑制乳腺癌侵袭与转移，逆转 上皮-间质转化（EMT）。通过miRNA芯片验证发现SS显著上调乳腺癌细胞miR-200b/c的表 达，下调miR-374a的表达。在乳腺癌中miR-374a可激活Wnt/β-catenin 通路促进EMT形成 。预实验显示Wnt1是miR-200b/c共同靶基因。综上提出科学假说：SS可改善肿瘤微环境( 包括EMT)，下调miR-374a，上调miR-200b/c共同阻断Wnt/β-catenin，进而实现抑制乳腺 癌转移。本项目采用qRT-PCR、Western blot、体内动物成像等技术从miRNA、肿瘤微环境 (EMT)等探讨SS抗乳腺癌侵袭转移的分子机制，为活血养血中药SS防治乳腺癌转移提供理论和实验依据。