Citation: | LIU Jianbo, LI Baiyu, KE Shanbao, ZHANG Wei. Cordycepin Attenuates Immune Function Injury in A Rat Model of Lung Cancer After Radiotherapy by Inhibiting JAK2/STAT3 Pathway[J]. Cancer Research on Prevention and Treatment, 2021, 48(11): 994-998. DOI: 10.3971/j.issn.1000-8578.2021.21.0094 |
To investigate the inhibitory effect of cordycepin on immune function injury in lung cancer rats after radiation therapy through JAK2/STAT3 signaling pathway.
Fifty 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.
Compared 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).
Cordycepin 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.
Competing interests: The authors declare that they have no competing interests.
[1] |
宋春洋, 祝淑钗, 沈文斌, 等. 临床Ⅲ期食管癌患者放疗前后免疫功能及外周血炎症指标对预后的影响分析[J]. 中华放射医学与防护杂志, 2020, 40(3): 189-195. doi: 10.3760/cma.j.issn.0254-5098.2020.03.006
Song CY, Zhu SC, Shen WB, et al. Analysis of the effects of immunity index and blood inflammatory markers pre- and post-radiotherapy on prognosis of clinical stage Ⅲ esophageal cancer patients[J]. Zhonghua Fang She Yi Xue Yu Fang Hu Za Zhi, 2020, 40(3): 189-195. doi: 10.3760/cma.j.issn.0254-5098.2020.03.006
|
[2] |
王多, 鲍荣, 王芳, 等. 虫草素抗肿瘤作用分子机制研究进展[J]. 中国药理学与毒理学杂志, 2015, 29(4): 643-650. doi: 10.3867/j.issn.1000-3002.2015.04.018
Wang D, Bao R, Wang F, et al. progress in molecular mechanisms of anticancer action of corycepin[J]. Zhongguo Yao Li Xue Yu Du Li Xue Za Zhi, 2015, 29(4): 643-650. doi: 10.3867/j.issn.1000-3002.2015.04.018
|
[3] |
Zhang Y, Zhang XX, Yuan RY, et al. Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo[J]. Onco Targets Ther, 2018, 11: 4479-4490. doi: 10.2147/OTT.S164670
|
[4] |
Wang C, Mao ZP, Wang L, et al. Cordycepin inhibits cell growth and induces apoptosis in human cholangiocarcinoma[J]. Neoplasma, 2017, 64(6): 834-839. doi: 10.4149/neo_2017_604
|
[5] |
Lin YT, Liang SM, Wu YJ, et al. Cordycepin suppresses endothelial cell proliferation, migration, angiogenesis, and tumor growth by regulating focal adhesion kinase and p53[J]. Cancers(Basel), 2019, 11(2): 168. http://www.onacademic.com/detail/journal_1000041694748599_3052.html
|
[6] |
韩丹, 崔琳琳, 王莹, 等. 虫草素药理作用研究进展[J]. 食品工业科技, 2019, 40(9): 335-338, 345. https://www.cnki.com.cn/Article/CJFDTOTAL-SPKJ201909057.htm
Han D, Cui LL, Wang Y, et al. Research Progress On Pharmacological Effects Of Cordycepin[J]. Shi Pin Gong Ye Ke Ji, 2019, 40(9): 335-338, 345. https://www.cnki.com.cn/Article/CJFDTOTAL-SPKJ201909057.htm
|
[7] |
Mao Y, Yang D, He J, et al. Epidemiology of lung cancer[J]. Surg Oncol Clin N Am, 2016, 25(3): 439-445. doi: 10.1016/j.soc.2016.02.001
|
[8] |
Michaelidesová A, Konířová J, Bartůněk P, et al. Effects of radiation therapy on neural stem cells[J]. Genes(Basel), 2019, 10(9): 640. http://www.ncbi.nlm.nih.gov/pubmed/31450566
|
[9] |
Kirova Y, Tallet A, Aznar MC, et al. Radio-induced cardiotoxicity: from physiopathology and risk factors to adaptation of radiotherapy treatment planning and recommended cardiac follow-up[J]. Cancer Radiother, 2020, 24(6-7): 576-585. doi: 10.1016/j.canrad.2020.07.001
|
[10] |
Weichselbaum RR, Liang H, Deng L, et al. Radiotherapy and immunotherapy: a beneficial liaison?[J]. Nat Rev Clin Oncol, 2017, 14(6): 365-379. doi: 10.1038/nrclinonc.2016.211
|
[11] |
Woolley VC, Teakle GR, Prince G, et al. Cordycepin, a metabolite of Cordyceps militaris, reduces immune-related gene expression in insects[J]. J Invertebr Pathol, 2020, 177: 107480. doi: 10.1016/j.jip.2020.107480
|
[12] |
Lei J, Wei Y, Song P, et al. Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress[J]. Eur J Pharmacol, 2018, 818: 110-114. doi: 10.1016/j.ejphar.2017.10.029
|
[13] |
Tan L, Song X, Ren Y, et al. Anti-inflammatory effects of cordycepin: A review[J]. Phytother Res, 2020. Online ahead of print.
|
[14] |
安青, 何立巍, 吴红雁, 等. 虫草素通过调节CD4+T淋巴细胞PD-1受体促进肿瘤免疫及机制研究[J]. 南京中医药大学学报, 2018, 34(5): 495-498. https://www.cnki.com.cn/Article/CJFDTOTAL-NJZY201805015.htm
An Q, He LW, Wu HY, et al. Mechanism of cordycepin promotes tumor immunity by regulating PD-1 receptor of CD4+T lymphocytes[J]. Nanjing Zhong Yi Yao Da Xue Xue Bao, 2018, 34(5): 495-498. https://www.cnki.com.cn/Article/CJFDTOTAL-NJZY201805015.htm
|
[15] |
Zundler S, Neurath MF. Integrating immunologic signaling networks: the JAK/STAT pathway in colitis and colitis-associated cancer[J]. Vaccines(Basel), 2016, 4(1): 5. http://www.onacademic.com/detail/journal_1000040540984510_5b25.html
|
[16] |
Yu T, Li Z, Xu L, et al. Anti-inflammation effect of Qingchang suppository in ulcerative colitis through JAK2/STAT3 signaling pathway in vitro and in vivo[J]. J Ethnopharmacol, 2021, 266: 113442. doi: 10.1016/j.jep.2020.113442
|
[17] |
Qing Y, Stark GR. Alternative activation of STAT1 and STAT3 in response to interferon-gamma[J]. J Biol Chem, 2004, 279(40): 41679-41685. doi: 10.1074/jbc.M406413200
|
[18] |
Lei RE, Shi C, Zhang PL, et al. IL-9 promotes proliferation and metastasis of hepatocellular cancer cells by activating JAK2/STAT3 pathway[J]. Int J Clin Exp Pathol, 2017, 10(7): 7940-7946. http://www.researchgate.net/publication/326058664_IL-9_promotes_proliferation_and_metastasis_of_hepatocellular_cancer_cells_by_activating_JAK2STAT3_pathway
|
[19] |
Chen J, Zhang W, Xu Q, et al. Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway[J]. Int J Mol Med, 2018, 41(5): 2865-2878. http://www.spandidos-publications.com/ijmm/41/5/2865/download
|