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甘草苷对胃癌荷瘤小鼠免疫功能的调节作用及机制研究
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兰春燕 ,杨小兰 ,贺雪峰 ,赵 丹 ,杨海燕 (1.达州中医药职业学院药学院,四川 达州 635000;2.成都中
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医药大学附属医院针灸学校中药教研室,成都 610000;3.达州市中西医结合医院临床药学科,四川 达州
635000)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2024)15-1862-06
DOI 10.6039/j.issn.1001-0408.2024.15.11
摘 要 目的 基于Janus激酶2(JAK2)/信号转导及转录激活蛋白3(STAT3)信号通路研究甘草苷(LIQ)对胃癌荷瘤小鼠免疫功
能的调节作用及机制。方法 皮下注射胃癌细胞MFC建立小鼠胃癌荷瘤模型,将造模成功的小鼠分为模型组(Model组)、低剂量
LIQ组(LIQ-L组,20 mg/kg)、高剂量LIQ组(LIQ-H组,40 mg/kg)、高剂量LIQ+JAK2激活剂香豆霉素A1组(LIQ-H+香豆霉素A1
组,40 mg/kg LIQ+1 mg/kg香豆霉素A1),每组12只;另取12只不造模小鼠设为正常组(Normal组)。各组小鼠灌胃/腹腔注射相应
药物或生理盐水,每日给药 1 次,连续 14 d。末次给药后,测定小鼠胃癌肿瘤的体积、质量以及脏器指数;检测外周血中 CD4 、
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CD8 T淋巴细胞百分率;观察胃癌肿瘤组织病理形态学变化;检测胃癌肿瘤组织中JAK2/STAT3信号通路相关蛋白和白细胞介素
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6(IL-6)蛋白表达水平。结果 与Normal组相比,Model组小鼠胸腺指数、脾脏指数、外周血中CD8 T淋巴细胞百分率均显著升高
(P<0.05),外周血中CD4 T淋巴细胞百分率显著降低(P<0.05)。与Model组相比,LIQ-L组、LIQ-H组小鼠上述指标均显著逆转
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(P<0.05),胃癌肿瘤的体积、质量以及肿瘤组织中 JAK2、STAT3 蛋白的磷酸化水平和 IL-6 蛋白的表达水平均显著降低(P<
0.05),且LIQ的作用具有剂量依赖性(P<0.05);肿瘤组织细胞出现不同程度的排列疏松、空泡化、分布不均匀等情况。加入JAK2
激活剂香豆霉素A1减弱了LIQ对胃癌荷瘤小鼠免疫功能的改善作用和对胃癌肿瘤的抑制作用(P<0.05)。结论 LIQ可通过抑制
JAK2/STAT3信号通路,改善胃癌荷瘤小鼠的免疫功能,从而发挥抗肿瘤作用。
关键词 甘草苷;JAK2/STAT3信号通路;胃癌;免疫功能
Regulation effects and mechanism of liquiritin on immune function in gastric cancer-bearing mice
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LAN Chunyan ,YANG Xiaolan ,HE Xuefeng ,ZHAO Dan ,YANG Haiyan(1. School of Pharmacy, Dazhou
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Vocational College of Chinese Medicine, Sichuan Dazhou 635000, China;2. Dept. of Traditional Chinese
Medicine, School of Acupuncture and Moxibustion, Hospital of Chengdu University of Traditional Chinese
Medicine, Chengdu 610000, China;3. Dept. of Clinical Pharmacology, Dazhou Hospital of Integrated
Traditional Chinese and Western Medicine, Sichuan Dazhou 635000, China)
ABSTRACT OBJECTIVE To study the regulation effects and mechanism of liquiritin (LIQ) on immune function in gastric
cancer-bearing mice based on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway.
METHODS Gastric cancer cells MFC were injected subcutaneously to establish gastric cancer-bearing model of mice. The model
mice were divided into model group, LIQ low-dose group (LIQ-L group, 20 mg/kg), LIQ high-dose group (LIQ-H group, 40
mg/kg), and high-dose LIQ+JAK2 activator coumermycin A1 group (LIQ-H+coumermycin A1 group, 40 mg/kg LIQ+1 mg/kg
coumermycin A1), with 12 mice in each group. Another 12 mice without modeling were set as normal group. Mice in each group
were given the corresponding drug or normal saline by intragastric administration/intraperitoneal injection, once a day, for
consecutive 14 days. After the last administration, the volume and mass of gastric cancer tumor and organ index were measured.
The percentages of CD4 and CD8 T lymphocytes were detected in peripheral blood. The histopathological morphology of gastric
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cancer tumor tissues was observed, and the expression levels
Δ 基金项目 四川省中医药管理局科学技术研究专项课题(No. of JAK2/STAT3 signaling pathway-related proteins and
2021MS208) interleukin-6 (IL-6) protein in gastric cancer tumor tissues
*第一作者 主管中药师。研究方向:中药炮制、中药药理。
were detected. RESULTS Compared with the normal group,
E-mail:lcy8882024@163.com
the thymus index, spleen index, and the percentage of CD8 T
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# 通信作者 讲师,硕士。研究方向:中药资源与中医药文化。
E-mail:yang9012012024@163.com lymphocyte in the peripheral blood of mice were obviously
· 1862 · China Pharmacy 2024 Vol. 35 No. 15 中国药房 2024年第35卷第15期