Yang Bing, Yu Gui-Hong, Li Ming-Yu, Gu Hui-Min, Chen Ya-Ping, Feng Liang, Jia Xiao-Bin
School of Traditional Chinese Pharmacy,China Pharmaceutical University Nanjing 211198,China Third Clinical Medical College,Nanjing University of Chinese Medicine Nanjing 210023,China.
School of Traditional Chinese Pharmacy,China Pharmaceutical University Nanjing 211198,China.
Zhongguo Zhong Yao Za Zhi. 2019 Dec;44(23):5184-5190. doi: 10.19540/j.cnki.cjcmm.20191104.401.
Traditional Chinese medicine believes that the occurrence and development of tumors is related to the body's Qi deficiency. " Invigorating Qi for consolidation of exterior" has became an effective way to treat tumors by traditional Chinese medicine. This study is based on the " invigorating Qi for consolidation of exterior" to explore the effect of flavonoid components in Qi-invigorating herbs Astragali Radix( AR) on the growth and immune function of mouse Lewis lung cancer xenografts,and further explore its mechanism of action. In the present study,high performance liquid chromatography was performed to analyze the flavonoid components in AR.The Lewis lung cancer model of C57 BL/6 mice was constructed,and the tumor volume of mice was determined by Visual Sonics Vevo2100 high frequency color ultrasound. The levels of IL(-1)7 and RORγt in serum and tumor tissues were detected by ELISA and immunohistochemistry. The expression of IRE(-1)/XBP(-1) pathway-related proteins in tumor tissues was detected by Western blot. The results revealed that treatment of 5 and 10 g·kg(-1)·d(-1) of flavonoid components in AR significantly inhibited tumor growth of C57 BL/6 tumorbearing mice. The inhibition rates at the dose of 5 and 10 g·kg(-1)·d(-1) of flavonoid components in AR were( 29. 5±4. 4) % and( 43. 4±5. 2) %,respectively. The expression of IL(-1)7 and RORγt in serum and tumor tissues of Lewis lung cancer mice were decreased,and the spleen index and thymus index were significantly enhanced by the flavonoid components in AR. Flavonoid components in AR could decrease the expression of X-box binding protein 1( XBP1),inositol-requiring enzyme( IRE1) and glucose regulated protein 78 k D( GRP78),and increase the expression of C/EBP homologous protein( CHOP),and the high-dose group is better,suggesting that the anti-lung cancer effect of flavonoid components in AR is related to the regulation of XBP1 mediated ERs. This study provides new evidence that the flavonoid components in AR could inhibit the tumor growth of C57 BL/6 tumor-bearing mice by regulating the body's immune function through " invigorating Qi for consolidation of exterior".
中医认为肿瘤的发生发展与机体气虚有关。“益气固表”成为中医治疗肿瘤的有效方法。本研究基于“益气固表”探讨益气中药黄芪中黄酮类成分对小鼠Lewis肺癌移植瘤生长及免疫功能的影响,并进一步探讨其作用机制。本研究采用高效液相色谱法分析黄芪中黄酮类成分。构建C57 BL/6小鼠Lewis肺癌模型,通过Visual Sonics Vevo2100高频彩色超声测定小鼠肿瘤体积。采用ELISA和免疫组化法检测血清及肿瘤组织中IL-17和RORγt水平。采用Western blot法检测肿瘤组织中IRE-1/XBP-1通路相关蛋白的表达。结果显示,黄芪中黄酮类成分5、10 g·kg-1·d-1剂量处理显著抑制C57 BL/6荷瘤小鼠肿瘤生长。黄芪中黄酮类成分5、10 g·kg-1·d-1剂量的抑瘤率分别为(29.5±4.4)%和(43.4±5.2)%。黄芪中黄酮类成分可降低Lewis肺癌小鼠血清及肿瘤组织中IL-17和RORγt的表达,显著提高脾脏指数和胸腺指数。黄芪中黄酮类成分可降低X盒结合蛋白1(XBP1)、肌醇需求酶(IRE1)和葡萄糖调节蛋白78 kD(GRP78)的表达,增加C/EBP同源蛋白(CHOP)的表达,高剂量组效果更佳,提示黄芪中黄酮类成分的抗肺癌作用与调节XBP1介导 的内质网有关。本研究为黄芪中黄酮类成分通过“益气固表”调节机体免疫功能抑制C57 BL/6荷瘤小鼠肿瘤生长提供了新证据。