益母草碱对结肠癌荷瘤小鼠肿瘤生长和免疫功能的影响OA北大核心CSTPCD
Impacts of leonurine on tumor growth and immune function in colon cancer bearing mice
目的 探讨益母草碱对结肠癌荷瘤小鼠肿瘤生长和免疫功能的影响.方法 C57BL/6小鼠建立结肠癌荷瘤小鼠模型,造模后的小鼠随机分为对照组(0.9%NaCl)、低剂量实验组(180 ng·g-1益母草碱)、高剂量实验组(360 ng·g-1益母草碱)、高剂量+空载组(360 ng·g-1益母草碱+空载质粒)、高剂量+cGAS敲低组(360 ng·g-1+cGAS siRNA质粒).分组处理后测定肿瘤体积与质量,以免疫组化染色检测肿瘤组织环状GMP-AMP合成酶(cGAS)、干扰素基因刺激因子(STING)相对阳性表达及CD4+T与CD8+T阳性细胞数,以细胞计数试剂盒8法检测小鼠CD4+T与CD8+T细胞对肿瘤细胞杀伤率.结果 对照组、高剂量实验组、高剂量+空载组、高剂量+cGAS敲低组小鼠的肿瘤体积分别为(1 088.32±70.82)、(468.20±24.28)、(480.01±23.78)和(998.99±32.84)mm3,cGAS 相对阳性表达分别为 1.00±0.00、5.18±0.73、5.30±0.80 和 1.12±0.46,STING 相对阳 性表达分别为 1.00±0.00、5.64±0.81、5.48±0.75 和 1.14±0.50,CD4+T 阳性细胞数分别为(40.25±5.82)、(118.64±15.30)、(113.25±16.65)和(48.74±7.10)个,CD8+T 阳性细胞数分别为(49.76±6.12)、(143.68±16.80)、(135.75±17.42)和(57.01±8.24)个.高剂量实验组、高剂量+空载组的上述指标与对照组比较,在统计学上差异均有统计学意义(均P<0.05);高剂量+cGAS敲低组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05).结论 益母草碱可通过激活cGAS-STING信号而增强结肠癌荷瘤小鼠淋巴细胞增殖能力,抑制小鼠肿瘤生长.
Objective To investigate the effects of leonurine on tumor growth and immune function of colon cancer tumor bearing mice.Methods C57BL/6 mice were established a colon cancer bearing mouse model.After modeling,the mice were randomly divided into control group(0.9%NaCl),experimental-L group(180 ng·g-1 leonurine),experimental-H group(360 ng·g-1 Leonurine),experimental-H+NC group(360 ng·g-1 leonurine+no-load plasmid),and experimental-H+sicGAS group(360 ng·g-1 leonurine+cGAS siRNA plasmid).Tumor volume and weight were measured after group treatment.Immunohistochemical staining was used to detect the relative positive expression of cyclic GMP-AMP synthase(cGAS),stimulator of interferon gene(STING)and the average positive number of CD4+T and CD8+T cells in tumor tissues.The killing rate of mouse CD4+T and CD8+T cells to tumor cells was detected by cell counting kit 8.Results The tumor volume of control group,experimental-H group,experimental-H+NC group and experimental-H+cGAS knockout group were(1 088.32±70.82),(468.20±24.28),(480.01±23.78)and(998.99±32.84)mm3,respectively;the relative positive expressions of cGAS were 1.00±0.00,5.18±0.73,5.30±0.80 and 1.12±0.46,respectively;the relative positive expressions of STING were 1.00±0.00,5.64±0.81,5.48±0.75 and 1.14±0.50,respectively;the mean CD4+T positive cells were 40.25±5.82,118.64±15.30,113.25±16.65 and 48.74±7.10,respectively;the average number of CD8+T positive cells were 49.76±6.12,143.68±16.80,135.75±17.42 and 57.01±8.24,respectively.The above indexes in experimental-H group and experimental-H+no-load group were statistically significant compared with control group(all P<0.05);there were statistically significant differences in the above indexes between the experimental-H+sicGAS group and the experimental-H group(all P<0.05).Conclusion Leonurine can enhance the proliferation ability of lymphocytes in colon cancer tumor bearing mice by activating cGAS-STING signal,and inhibit tumor growth in mice.
刘建邦;黄娟;李斌
中国人民解放军联勤保障部队第九二○医院普外科,云南昆明 650032
中医学
益母草碱环状GMP-AMP合成酶/干扰素基因刺激因子结肠癌荷瘤肿瘤生长免疫功能
leonurinecyclic GMP-AMP synthetase/stimulator of interferon genecolon cancertumor bearingtumor growthimmune function
《中国临床药理学杂志》 2024 (003)
398-402 / 5
国家卫生健康委"十四五"规划全国重点课题基金资助项目(YYWS2810)
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