加味四君子汤对小鼠CT26大肠癌移植瘤的抑制作用及肿瘤相关巨噬细胞CD68、CD206蛋白表达的影响
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摘要
目的:观察加味四君子汤对小鼠CT26大肠癌移植瘤的抑制作用及肿瘤相关巨噬细胞CD68、CD206蛋白表达的影响。方法:取大肠癌CT26细胞体外培养,建立BALB/C小鼠大肠癌皮下移植瘤模型。取造模成功的BALB/C小鼠随机分为模型组和加味四君子汤低、中、高剂量组,每组5只。加味四君子汤各组小鼠分别灌胃给予0.035、0.07、0.14 g/g药液,模型组小鼠灌胃给予等体积0.9%NaCl溶液,连续21 d。末次给药后,剥离瘤体,测量移植瘤体积并计算抑瘤率;免疫组化检测各组小鼠瘤体组织中肿瘤相关巨噬细胞CD68和CD206的蛋白表达。结果:药物干预21 d后,与模型组相比,加味四君子汤中剂量组小鼠的移植瘤体积显著减小(P<0.05),肿瘤生长抑制率显著升高(P<0.05),且其抑瘤效果明显优于低、高剂量组(P<0.05)。免疫组化观察显示,与模型组相比,加味四君子汤中剂量组小鼠瘤体组织内肿瘤相关巨噬细胞CD68和CD206表达显著降低(P<0.01);且中剂量组对CD68和CD206表达的抑制作用明显强于低、高剂量组(P<0.05,P<0.01)。结论:加味四君子汤能有效抑制小鼠CT26大肠癌移植瘤生长,其作用机制可能与下调肿瘤相关巨噬细胞CD68和CD206的表达有关。
Objective: To observe the inhibitory effects of Modified Sijunzi Decoction on the transplanted tumor of CT26 colorectal cancer in mice and the influence on the expressions of tumor-associated macrophages CD68 and CD206.Methods: The colorectal cancer cell line CT26 was cultured in vitro,and the subcutaneous transplanted tumor model of colorectal cancer was established in BALB/C mice. The successful modeling mice were taken and randomly divided into the model group and Modified Sijunzi Decoction groups with low-,middle-and high-dose,5 mice in each group. The Modified Sijunzi Decoction groups were treated with the decoction at dose of 0.035 g/g,0.07 g/g and 0.14 g/g respectively,and the model group was treated with 0.9% NaCl solution at equivalent volume,with a course of continuous 21 days. After the last administration,the tumor was isolated. The transplanted tumor volume was measured and the inhibition rate was calculated. The protein expressions of tumor-associated macrophages CD68 and CD206 in tumor tissue were detected by immunohistochemistry. Results: After drug treatment for 21 days,the tumor volume was significantly decreased in the Modified Sijunzi Decoction group with middle-dose(P<0.05),and the inhibition rate on tumor growth was significantly increased(P<0.05),and the inhibitory effect of the middle-dose group was obviously better than that of the low-dose group and high-dose group. The results of immunohistochemisry indicated that,compared with the model group,the expressions of CD68 and CD206 in tumor tissue were significantly decreased in the Modified Sijunzi Decoction group with middle-dose(P<0.01). The inhibition on CD68 and CD206 expressions in the middle-dose group was obviously stronger than that in the low-and high-dose group( P < 0.05,P < 0.01). Conclusion: Modified Sijunzi Decoction can effectively inhibit the transplanted tumor growth of CT26 colorectal cancer in mice,and its mechanism may be related to down-regulating the expressions of tumor-associated macrophages CD68 and CD206.
Objective: To observe the inhibitory effects of Modified Sijunzi Decoction on the transplanted tumor of CT26 colorectal cancer in mice and the influence on the expressions of tumor-associated macrophages CD68 and CD206.Methods: The colorectal cancer cell line CT26 was cultured in vitro,and the subcutaneous transplanted tumor model of colorectal cancer was established in BALB/C mice. The successful modeling mice were taken and randomly divided into the model group and Modified Sijunzi Decoction groups with low-,middle-and high-dose,5 mice in each group. The Modified Sijunzi Decoction groups were treated with the decoction at dose of 0.035 g/g,0.07 g/g and 0.14 g/g respectively,and the model group was treated with 0.9% NaCl solution at equivalent volume,with a course of continuous 21 days. After the last administration,the tumor was isolated. The transplanted tumor volume was measured and the inhibition rate was calculated. The protein expressions of tumor-associated macrophages CD68 and CD206 in tumor tissue were detected by immunohistochemistry. Results: After drug treatment for 21 days,the tumor volume was significantly decreased in the Modified Sijunzi Decoction group with middle-dose(P<0.05),and the inhibition rate on tumor growth was significantly increased(P<0.05),and the inhibitory effect of the middle-dose group was obviously better than that of the low-dose group and high-dose group. The results of immunohistochemisry indicated that,compared with the model group,the expressions of CD68 and CD206 in tumor tissue were significantly decreased in the Modified Sijunzi Decoction group with middle-dose(P<0.01). The inhibition on CD68 and CD206 expressions in the middle-dose group was obviously stronger than that in the low-and high-dose group( P < 0.05,P < 0.01). Conclusion: Modified Sijunzi Decoction can effectively inhibit the transplanted tumor growth of CT26 colorectal cancer in mice,and its mechanism may be related to down-regulating the expressions of tumor-associated macrophages CD68 and CD206.
引文
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[2] 董晶,陆宁,史国军. 复方藤梨根制剂联合XELIRI方案治疗结肠癌晚期肝转移的临床研究[J].中国中医药科技,2017,24(2):132- 134.
[3] 靳祎祎,严兆坤,赖子君,等. 白花蛇舌草对大肠癌耐药移植瘤细胞凋亡的影响[J].现代中西医结合杂志,2017,26(12):1255- 1258.
[4] 李进安,王永多,王奎,等. 四君子汤对结肠癌术后患者胃肠恢复及免疫功能作用研究[J].实用癌症杂志,2016,31(6):1034- 1036.
[5] 李瑞芝,马浩清,金晓董,等. 加味四君子汤对结肠癌细胞SW620增殖和凋亡的影响[J].浙江中医杂志,2015,50(7):487- 489.
[6] MARECH I,AMMENDOLA M,SACCO R,et al. Tumor- associated macrophages correlate with microvascular bed extension in colorectal cancer patients[J].J Cell Mol Med,2016,20(7):1373- 1380.
[7] RHEE I. Diverse macrophages polarization in tumor microenvironment[J].Arch Pharm Res,2016,39(11):1588- 1596.
[8] YANG M,LIU J,SHAO J,et al. Cathepsin S- mediated autophagic flux in tumor- associated macrophages accelerate tumor development by promoting M2 polarization[J].Mol Cancer,2014,13(24):1680- 1695.
[9] UBIL E,CASKEY L,HOLTZHAUSEN A,et al. Tumor- secreted Pros1 inhibits macrophage M1 polarization to reduce antitumor immune response[J].J Clin Invest,2018,128(6):2356- 2369.
[10] ZHOU D,HUANG C,LIN Z,et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways[J].Cell Signal,2014,26(2):192- 197.
[11] KOMOHARA Y,FUJIWARA Y,OHNISHI K,et al. Tumor- associated macrophages:Potential therapeutic targets for anti- cancer therapy[J].Adv Drug Deliv Rev,2016,99(Pt B):180- 185.