Sun Ruo-Lan, Tang De-Cai, Gu Jun-Fei
School of Traditional Chinese Medicine·School of Integrated Chinese and Western Medicine,Nanjing University of Chinese Medicine Nanjing 210023, China.
Zhongguo Zhong Yao Za Zhi. 2021 May;46(9):2267-2275. doi: 10.19540/j.cnki.cjcmm.20201207.402.
Astragali Radix-Curcumae Rhizoma is a classic drug pair mainly used for the treatment of digestive tract-related inflammation and tumors, but the ratio is not fixed in clinical practice. In order to study whether the anti-tumor effect of the drug pair is diffe-rent under different ratios, orthotopic transplantation model of colon cancer was established in mice. Then the principal component analysis(PCA) and cluster analysis(CA) were used to explore the effect of different ratios of the drug pair on the tumor growth and metastasis, and select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. After administration for 15 days, the body weight of colon cancer mice with the tumor removed, the tumor volume and the number of liver metastases were mea-sured; the pathological changes of tumor tissue and liver tissue were observed by HE staining. At the same time, Western blot method was used to detect the protein expression level of tumor growth-related indicators in tumor tissue(Ki67, HBP1, AFP) and tumor metastasis-related indicators in liver tissue(β-catenin, E-cadherin, vimentin, p53) of the tumor-bearing mice. Subsequently, PCA and CA were used to select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. The experimental results showed that different ratios of Astragali Radix-Curcumae Rhizoma inhibited tumor growth and metastasis to varying degrees. The ratio at 1∶1 of Astragali Radix-Curcumae Rhizoma had the best inhibitory effect on tumor growth, and the 2∶1 ratio group had the best effect on inhibiting liver metastasis and improving weighed loss. Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of HBP1 in tumor tissue of colon cancer mice, and significantly down-regulated the protein expression of Ki67 and AFP in tumor tissue; meanwhile, Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of E-cadherin in liver tissue of colon cancer mice, and significantly reduced the protein expression of β-catenin, vimentin and p53 in liver tissue. PCA results showed that the first three groups in the Astragali Radix-Curcumae Rhizoma compatibility group that were closer to the sham operation group were in the order of 2∶1, 1∶1 and 3∶2, among which the center distance of the 2∶1 group was the shortest from the sham operation group, indicating that the ratio 2∶1 of Astragali Radix-Curcumae Rhizoma had the best intervention effect on colon cancer in mice, consistent with the commonly used clinical proportion. CA results showed that 11 groups of colon cancer mice were classified into 3 categories: Astragali Radix-Curcumae Rhizoma compatibility group, sham operation group and model group, which was consistent with the theory. The results of this study provide a basis for more effective clinical application of Astragali Radix-Curcumae Rhizoma in the treatment of colon cancer, and provide new ideas for the development of classic drug pairs.
黄芪 - 莪术是一对经典药对,主要用于治疗消化道相关炎症和肿瘤,但在临床应用中其配比并不固定。为研究该药对在不同配比下的抗肿瘤效果是否存在差异,在小鼠体内建立了结肠癌原位移植模型。然后运用主成分分析(PCA)和聚类分析(CA),探究药对不同配比在肿瘤生长和转移方面的作用,并筛选出黄芪 - 莪术抗结肠癌效果的最佳配比。给药15天后,测量切除肿瘤的结肠癌小鼠体重、肿瘤体积及肝转移灶数量;通过苏木精 - 伊红(HE)染色观察肿瘤组织和肝组织的病理变化。同时,采用蛋白质免疫印迹法检测荷瘤小鼠肿瘤组织中肿瘤生长相关指标(Ki67、HBP1、AFP)及肝组织中肿瘤转移相关指标(β - 连环蛋白、E - 钙黏蛋白、波形蛋白、p53)的蛋白表达水平。随后,运用PCA和CA筛选出黄芪 - 莪术抗结肠癌效果的最佳配比。实验结果表明,不同配比的黄芪 - 莪术对肿瘤生长和转移均有不同程度的抑制作用。黄芪 - 莪术1∶1配比组对肿瘤生长的抑制作用最佳,2∶1配比组对抑制肝转移和改善体重减轻效果最佳。黄芪 - 莪术显著上调结肠癌小鼠肿瘤组织中HBP1的蛋白表达,显著下调肿瘤组织中Ki67和AFP的蛋白表达;同时,黄芪 - 莪术显著上调结肠癌小鼠肝组织中E - 钙黏蛋白的蛋白表达,显著降低肝组织中β - 连环蛋白、波形蛋白和p53的蛋白表达。PCA结果显示,黄芪 - 莪术配伍组中与假手术组距离较近的前三组依次为2∶1、1∶1和3∶2,其中2∶1组与假手术组的中心距离最短,表明黄芪 - 莪术2∶1配比在干预小鼠结肠癌方面效果最佳,与临床常用比例相符。CA结果显示,11组结肠癌小鼠分为3类:黄芪 - 莪术配伍组、假手术组和模型组,与理论相符。本研究结果为黄芪 - 莪术在结肠癌治疗中更有效的临床应用提供了依据,也为经典药对的开发提供了新思路。