[关键词]
[摘要]
目的 探讨鸦胆子苦醇调节环磷酸鸟苷-腺苷酸合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对肝癌H22荷瘤小鼠肿瘤生长及免疫功能的影响。方法 通过左前肢腋窝sc接种H22细胞建立荷瘤小鼠模型,随机分为模型组,鸦胆子苦醇低、中、高剂量(0.916、1.832、3.664 mg·kg-1,ig给药)组,鸦胆子苦醇(3.664 mg·kg-1,ig给药)+RU.521(5 mg·kg-1,ip给药)组。干预结束后,取胸腺、脾脏、肿瘤称质量,测定小鼠胸腺和脾脏指数、抑瘤率;T淋巴细胞转化实验检测T淋巴细胞增殖指数;检测巨噬细胞吞噬鸡红细胞的能力;收集血清,试剂盒法检测白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平;Western blotting法检测肿瘤组织中cGAS、STING蛋白表达水平。结果 与对照组相比,模型组小鼠胸腺和脾脏指数、吞噬指数、吞噬百分率、T淋巴细胞增殖指数、IL-2和TNF-α水平显著下降(P<0.05);与模型组相比,鸦胆子苦醇低、中、高剂量组小鼠胸腺和脾脏指数、吞噬指数、吞噬百分率、T淋巴细胞增殖指数、IL-2和TNF-α水平、cGAS和STING蛋白表达显著增加(P<0.05),瘤质量显著降低(P<0.05),且作用均呈现剂量相关性;与鸦胆子苦醇高剂量组相比,鸦胆子苦醇+RU.521组胸腺和脾脏指数、吞噬指数、吞噬百分率、T淋巴细胞增殖指数、IL-2和TNF-α水平、cGAS和STING蛋白表达显著下降(P<0.05),瘤质量显著增加(P<0.05)。结论 鸦胆子苦醇通过激活cGAS-STING信号通路抑制肝癌H22荷瘤小鼠肿瘤生长,增强其免疫功能。
[Key word]
[Abstract]
Objective To investigate the impacts of brusatol on tumor growth and immune function of H22 hepatoma bearing mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene (STING) signal pathway. Methods The H22 tumor-bearing mice model was established by subcutaneous inoculation of H22 in the left forearm armpit. They were randomly grouped into model group, brusatol low, medium, high dose (0.916, 1.832, and 3.664 mg·kg-1) group, and brusatol (3.664 mg·kg-1) + cGAS inhibitor RU. 521 (5 mg·kg-1) group. After the intervention, the thymus, spleen, and tumor were weighed, and the thymus and spleen indices and tumor inhibition rate of the mice were measured. Detection of T lymphocyte proliferation index using T lymphocyte transformation assay. Detect the ability of macrophages to engulf chicken red blood cells. Collect serum and detect interleukin-2 (IL-2) and tumor necrosis factor-α (TNF- α) using a kit method. Western blotting method was used to detect the expression levels of cGAS and STING proteins in tumor tissue. Results Compared with the control group, the thymus index, spleen index, phagocytic index, phagocytic percentage, proliferative index, the levels of IL-2 and TNF-α in the model group were significantly decreased (P< 0.05). Compared with the model group, the thymus index, spleen index, phagocytic index, phagocytic percentage, proliferative index, the levels of IL-2 and TNF- α, the expression of cGAS and STING in brusatol low, medium, high dose groups were significantly increased, the tumor weight was significantly decreased, and showed a dose-dependent relationship between groups (P< 0.05). Compared with brusatol high dose group, the thymus index, spleen index, phagocytic index, phagocytic percentage, proliferative index, the levels of IL-2 and TNF-α, the expression of cGAS and STING in brusatol high dose group + RU. 521 group were significantly decreased, the tumor weight were significantly increased (P< 0.05). Conclusion Brusatol can inhibit tumor growth and enhance immune function of H22 hepatoma bearing mice by activating cGAS-STING signal pathway.
[中图分类号]
R285.5
[基金项目]
2020年度五官医学院专项科研基金项目(2020WG07)