香菇beta葡聚糖通过影响核受体nur77抑制乳腺癌的机制研究

Breast cancer is the most common malignant tumor that seriously threatens the life and health of women in the world. Many recent studies have shown that LNT not only plays a simple role in regulating the immune system in the treatment of breast cancer and other malignant tumors, but may be involved in interfering with the occurrence and development of tumors.The recent research shows that abnormal regulation of the orphan nuclear receptor Nur77 in immune cells is closely related to the a variety of malignant tumor development, In our initial work,we happen to find that LNT, stimulated by inflammatory factor TNFα, can induce apoptosis of human breast cancer cells and inhibit the growth of breast tumors in MMTV-PyMT transgenic mice by inhibiting the expression of Nur77 protein, inducing mitochondrial autophagy, and inhibiting the p62/mTOR signaling pathway.Therefore, it was predicted that regulation of LNT on the orphan nuclear receptor Nur77 has innate immunity dependence. This project intends to deeply explore how LNT regulates apoptosis, autophagy and p62/mTOR signaling pathway through the orphan nuclear receptor Nur77, and The project would ground the further development of new treatment strategies of anti- breast cancer drugs，has the good theoretical research value.

乳腺癌是全球女性中最为常见并且严重威胁女性生命健康的恶性肿瘤，近期很多研究提示香菇β-葡聚糖在治疗乳腺癌等恶性肿瘤中不仅限于简单的调节免疫作用，可能参与干扰肿瘤的发生发展，但目前尚无深入机制研究结果。近期有研究表明，孤儿核受体Nur77对免疫细胞功能的异常调节与多种恶性肿瘤的发生发展密切相关，我们前期研究发现香菇β-葡聚糖在TNFα介导下才可抑制Nur77表达、诱导自噬、抑制p62/mTOR信号通路并诱导人类乳腺癌细胞的凋亡，单用对免疫系统正常的MMTV-PyMT转基因乳腺癌小鼠有显著疗效。为此预测香菇β-葡聚糖影响孤儿核受体Nur77表达具有先天免疫依赖性。因此，本项目拟通过分子、细胞、整体动物等多个层面深入探讨香菇β-葡聚糖如何通过孤儿核受体Nur77调控凋亡、自噬以及p62/mTOR信号通路抗乳腺癌作用机制，为一类基于新靶点抗乳腺癌药物的研发提供重要依据，具有良好理论和应用研究价值。

乳腺癌是全球女性中最为常见并且严重威胁女性生命健康的恶性肿瘤，近期很多研究说明香菇β-葡聚糖在治疗乳腺癌等恶性肿瘤中不仅是简单的调节免疫作用，可能参与干扰肿瘤的发生发展，但目前尚无深入的机制研究结果。而近期研究表明，孤儿核受体Nur77对免疫细胞功能的异常调节与多种恶性肿瘤的发生发展密切相关，而我们又恰巧发现香菇β-葡聚糖只有在炎症因子刺激下才可以抑制Nur77蛋白表达、诱导自噬、抑制p62/mTOR信号通路并诱导人类乳腺癌细胞的凋亡，对MMTV-PyMT转基因乳腺癌小鼠也有显著疗效。为此预测香菇β-葡聚糖影响孤儿核受体Nur77表达具有天然免疫依赖性。因此，本项目拟通过分子、细胞、整体动物等多个层面深入探讨香菇β-葡聚糖如何通过孤儿核受体Nur77调控凋亡、自噬以及p62/mTOR信号通路抗乳腺癌作用机制，为一类基于新靶点抗乳腺癌药物的研发提供重要依据，具有良好的理论研究价值。