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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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| 篇名： | 甘草苷对胃癌荷瘤小鼠免疫功能的调节作用及机制研究 |
| TITLE： | Regulation effects and mechanism of liquiritin on immune function in gastric cancer-bearing mice |
| 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，20mg/kg）、高剂量LIQ组（LIQ-H组，40mg/kg）、高剂量LIQ+JAK2激活剂香豆霉素A1组（LIQ-H+香豆霉素A1组，40mg/kgLIQ+1mg/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14d。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+、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（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。 |
| 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 cancer tumor tissues was observed， and the expression levels of JAK2/STAT3 signaling pathway-related proteins and interleukin-6 （IL-6） protein in gastric cancer tumor tissues were detected. RESULTS Compared with the normal group， the thymus index， spleen index， and the percentage of CD8 T lymphocyte in the peripheral blood of mice were obviouslyincreased in model group （P＜0.05）， while the percentage of CD4+T lymphocyte in the peripheral blood were decreased （P＜0.05）. Compared with model group， the above indexes in LIQ-L group and LIQ-H group were significantly reversed （P＜0.05）， while the volume and mass of gastric cancer tumor， the phosphorylation levels of JAK2 and STAT3 protein and the expression level of IL-6 protein were significantly decreased in tumor tissue （P＜0.05）， and the effect of LIQ was in a dose-dependent manner （P＜0.05）； the tumor cells showed varying degrees of loose arrangement， vacuolization， and uneven distribution. JAK2 activator coumermycin A1 weakened the improvement effect of LIQ on the immune function of gastric cancer-bearing mice and its inhibitory effect on gastric cancer tumors （P＜0.05）. CONCLUSIONS LIQ can improve the immune function of gastric cancer-bearing mice by inhibiting the activation of JAK2/STAT3 signaling pathway， thus playing an anti-tumor role. |
| 期刊： | 2024年第35卷第15期 |
| 作者： | 兰春燕；杨小兰；贺雪峰；赵丹；杨海燕 |
| AUTHORS： | LAN Chunyan，YANG Xiaolan，HE Xuefeng，ZHAO Dan，YANG Haiyan |
| 关键字： | 甘草苷；JAK2/STAT3信号通路；胃癌；免疫功能 |
| KEYWORDS： | liquiritin； JAK2/STAT3 signaling pathway； gastric cancer； immune function |
| 阅读数： | 2 次 |
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