Cordycepin Attenuates Immune Function Injury in A Rat Model of Lung Cancer After Radiotherapy by Inhibiting JAK2/STAT3 Pathway
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摘要:目的
探讨虫草素通过JAK2/STAT3信号通路对肺癌大鼠放射性治疗免疫功能损伤的抑制作用。
方法50只大鼠建立荷瘤模型，另设正常组（10只）。建模成功大鼠随机分为模型组、放疗组、虫草素组、激动剂组和激动剂+虫草素组，每组10只。比较各组大鼠瘤重、肿瘤体积、抑瘤率、IL-6、TNF-α、脾指数、胸腺指数、T淋巴细胞亚群数量、JAK2、p-JAK2、STAT3和p-STAT3蛋白表达水平。
结果与正常组比较，模型组IL-6、TNF-α、CD8+、p-JAK2、p-STAT3升高，脾指数、胸腺指数、CD4+、CD4+/CD8+降低（P < 0.05）；与模型组比较，放疗组瘤重、肿瘤体积、脾指数、胸腺指数、CD4+、CD4+/CD8+降低，IL-6、TNF-α、CD8+、p-JAK2和p-STAT3升高（P < 0.05）；与放疗组比较，虫草素组瘤重、肿瘤体积、IL-6、TNF-α、CD8+、p-JAK2、p-STAT3降低，抑瘤率、脾指数、胸腺指数、CD4+、CD4+/CD8+升高，激动剂组瘤重、肿瘤体积、IL-6、TNF-α、CD8+、p-JAK2、p-STAT3升高，抑瘤率、脾指数、胸腺指数、CD4+、CD4+/CD8+降低（P < 0.05）；与激动剂+虫草素组比较，虫草素组瘤重、肿瘤体积、IL-6、TNF-α、CD8+、p-JAK2、p-STAT3降低，抑瘤率、脾指数、胸腺指数、CD4+、CD4+/CD8+升高，激动剂组瘤重、肿瘤体积、IL-6、TNF-α、CD8+、p-JAK2、p-STAT3升高，抑瘤率、脾指数、胸腺指数、CD4+、CD4+/CD8+降低（P < 0.05）。
结论虫草素可有效抑制肺癌大鼠放射性治疗免疫功能损伤，其机制可能通过抑制JAK2/STAT3信号通路蛋白表达发挥调控作用。
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关键词:
- 虫草素 /
- 放疗 /
- 免疫功能 /
- JAK2/STAT3
Abstract:ObjectiveTo investigate the inhibitory effect of cordycepin on immune function injury in lung cancer rats after radiation therapy through JAK2/STAT3 signaling pathway.
MethodsFifty rats were used to establish tumor-bearing model and other 10 rats were taken as normal group. After successful modeling, the rats were randomly divided into model group, radiotherapy group, cordycepin group, agonist group and agonist+cordycepin group (10 rats in each group). We compared tumor weight, tumor volume, tumor inhibition rate, IL-6, TNF-α, spleen index and thymus index, the number of T lymphocyte subsets, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression levels among all groups.
ResultsCompared with normal group, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 in model group were increased, while spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with model group, tumor weight, tumor volume, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased in radiotherapy group, while IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased (P < 0.05). Compared with radiotherapy group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 protein expression were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with agonist+cordycepin group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05).
ConclusionCordycepin can effectively inhibit the immune function injury in lung cancer rats after radiation therapy, and may play a regulatory role by inhibiting the JAK2/STAT3 signal pathway.
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Key words:
- Cordycepin /
- Radiation therapy /
- Immune function /
- JAK2/STAT3
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Competing interests: The authors declare that they have no competing interests.作者贡献：刘建波：实验设计及论文撰写李白羽：实验实施和资料收集柯善保：论文撰写张伟：论文修订和审校
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图 2 脾脏组织中JAK2、p-JAK2、STAT3和p-STAT3蛋白表达水平
Figure 2 Protein levels of JAK2, p-JAK2, STAT3 and p-STAT3 in spleen of rats
表 1 各组大鼠瘤重、肿瘤体积和抑瘤率比较(x±s)
Table 1 Comparison of tumor weight, tumor volume and tumor inhibition rate of rats among five groups (x±s)
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表 2 各组大鼠血清IL-6和TNF-α水平比较(x±s)
Table 2 Comparison of IL-6 and TNF-α levels in serum of rats among all groups (x±s)
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表 3 各组大鼠脾指数和胸腺指数比较(x±s)
Table 3 Comparison of spleen index and thymus index among all groups (x±s)
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表 4 各组大鼠脾脏T淋巴细胞亚群数量比较(x±s)
Table 4 Comparison of T lymphocyte subsets number in spleen of rats among all groups (x±s)
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表 5 脾脏组织中JAK2、p-JAK2、STAT3和p-STAT3蛋白表达(x±s)
Table 5 Comparison of JAK2, p-JAK2, STAT3 and p-STAT3 protein levels in spleen of rats among all groups (x±s)
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