1. 上海中医药大学附属曙光医院肿瘤科,上海,201203
2. 新疆医科大学附属中医医院肿瘤一科,新疆乌鲁木齐,830016
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王婷, 王巧琳, 段春燕, 等. 益气复生方联合化疗对胃癌荷瘤小鼠肿瘤生长及肿瘤浸润淋巴细胞的影响[J]. 上海中医药杂志, 2019,53(7):60-65.
WANG Ting, WANG Qiaolin, DUAN Chunyan, et al. Effects of Yiqi Fusheng Recipe combined with chemotherapy on tumor growth and tumor infiltrating lymphocytes in tumor-bearing mice with gastric cancer[J]. Shanghai Journal of Traditional Chinese Medicine, 2019,53(7):60-65.
王婷, 王巧琳, 段春燕, 等. 益气复生方联合化疗对胃癌荷瘤小鼠肿瘤生长及肿瘤浸润淋巴细胞的影响[J]. 上海中医药杂志, 2019,53(7):60-65. DOI: 10.16305/j.1007-1334.2019.07.016.
WANG Ting, WANG Qiaolin, DUAN Chunyan, et al. Effects of Yiqi Fusheng Recipe combined with chemotherapy on tumor growth and tumor infiltrating lymphocytes in tumor-bearing mice with gastric cancer[J]. Shanghai Journal of Traditional Chinese Medicine, 2019,53(7):60-65. DOI: 10.16305/j.1007-1334.2019.07.016.
目的:观察益气复生方(YQFS)联合化疗对胃癌荷瘤小鼠体内肿瘤微环境中肿瘤浸润淋巴细胞的影响,探讨YQFS联合化疗对胃癌荷瘤小鼠肿瘤生长的作用机制。 方法:雄性昆明小鼠腋下接种小鼠MFC胃癌细胞,建立小鼠荷瘤模型,分为空白对照组、模型组、5-FU+YQFS低剂量组、5-FU+YQFS高剂量组和5-FU组5组。空白对照组不作处理,模型组给予0.9%NaCl溶液灌胃,5-FU+YQFS低剂量组和5-FU+YQFS高剂量组给予5-FU腹腔注射7天和不同剂量益气复生方灌胃21天,5-FU组给予5-FU腹腔注射7天,21天后取材,对MFC胃癌荷瘤小鼠肿瘤组织和脾脏称重,计算抑瘤率和脾脏指数;采用流式细胞技术检测肿瘤浸润淋巴细胞CD4,+,、CD8,+,细胞亚群水平和比例;采用ELISA法检测外周血中IFN-γ、TNF-α、IL-10和IL-6的表达变化;采用组织切片HE染色观察小鼠胃黏膜的病理改变。 结果:YQFS联合化疗对胃癌荷瘤小鼠的抑瘤率为54.46%,与单用化疗相比,差异明显;YQFS联合化疗能够改变胃黏膜形态,降低脾脏指数。并且随着YQFS浓度的增加而降低,具有剂量依赖性(P,<,0.05)。与模型组相比,YQFS联合化疗能够增加肿瘤浸润淋巴细胞CD4,+,/CD8,+,比率;增加胃癌荷瘤小鼠外周血中的IFN-γ的表达,降低IL-10、IL-6、TNF-α的表达,并且与YQFS的浓度呈剂量依赖性变化。 结论:YQFS的抗肿瘤作用可能与增加荷瘤小鼠肿瘤浸润淋巴细胞CD4,+,/CD8,+,比率,降低小鼠脾脏指数,使外周血中的IFN-γ上调而IL-10、IL-6、TNF-α下调,恢复肿瘤免疫功能稳态,提高免疫力有关。
Objective:To observe the effects of Yiqi Fusheng Recipe (YQFS) combined with chemotherapy on tumor infiltrating lymphocytes in the tumor microenvironment, and to explore the mechanism of action of YQFS combined with chemotherapy on tumor growth in tumor-bearing mice with gastric cancer. MethodsThe MFC gastric cancer cells were inoculated to mice under the armpit, and the tumor bearing model of mice was established. The mice were divided into five groups, namely blank control group, model group, 5-FU + low-dose YQFS group, 5-FU + high-dose YQFS group and 5-FU group. The blank control group was not treated, the model group was given 0.9% NaCl solution by gastric gavage, the 5-FU + low-dose and 5-FU+ high-dose YQFS groups were given 5-FU intraperitoneal injection for 7 days and different doses of YQFS by gastric gavage for 21 days, and the 5-FU group was given 5-FU intraperitoneal injection for 7 days. Materials were taken after 21 days, the tumor tissue and spleen of tumor-bearing mice with MFC gastric cancer were weighed to calculate the tumor inhibition rate and the spleen index. The levels and proportions of CD4 and CD8 subsets in tumor infiltrating lymphocytes were detected by flow cytometry. The changes in expression of IFN-γ, TNF-α, IL-10 and IL-6 in peripheral blood were detected by ELISA. Pathological changes of gastric mucosa in mice were observed by HE staining of tissue sections. Results:The inhibition rate of YQFS combined with chemotherapy was 54.46% in tumor-bearing mice with gastric cancer, significantly different from that of chemotherapy alone. YQFS combined with chemotherapy could change the shape of gastric mucosa and reduce spleen index, which decreased with increase in YQFS concentration in a dose-dependent manner (P,<,0.05). Compared with the model group, YQFS combined with chemotherapy could increase the ratio of CD4,+,/CD8,+, in tumor infiltrating lymphocytes and the proportion of CD4,+,; it could also increase the expression of INF-γ in peripheral blood of tumor-bearing mice with gastric cancer, and reduce the expression of IL-10, IL-6 and TNF-α, showing dose-dependent changes with the concentration of YQFS. Conclusion:The anti-tumor effects of YQFS combined with chemotherapy may be related to increase of the CD4,+,/CD8,+, ratio in tumor infiltrating lymphocytes, decrease in spleen index, up-regulation of INF-γ and down-regulation of IL-10, IL-6 and TNF-α in peripheral blood, recovery of tumor immunization homeostasis and improvement of immunity in tumor-bearing mice with gastric cancer.
益气复生方胃癌肿瘤浸润细胞免疫CD4+/CD8
Yiqi Fusheng Recipegastric cancertumor infiltrating cellsimmunityCD4+/CD8
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