Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (4): 43-50.doi: 10.6040/j.issn.1671-7554.0.2017.1010

Previous Articles    

Total saponins of Panax ginseng promoting the anticancer activity of 5-Fluorouracil by mediating NK cell activity

MA Ranran1, HAN Chen2, WANG Zhaoxia2, WANG Zhaopeng2, GAO Yuxin2, ZHOU Shuping2, ZHANG Yueying2, LI Xiaobing2, LIU Hengyao1, WANG Hengxiao2   

  1. 1. School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250062, Shandong, China;
    2. Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, Shandong, China
  • Published:2022-09-27

PDF (PC)

8

Abstract: Objective To explore the inhibitory effects of total saponins of Panax ginseng(TSPG)combined with 5-fluorouracil(5-Fu)on orthotopic transplantation tumors and the mechanism. Methods The orthotopic transplantation tumor models were established and randomly divided into 4 groups: model group, TSPG group, 5-Fu group and TSPG+5-Fu group. After 14 days, the livers were harvested and tumors were separated. The tumor weight, volume and tumor inhibition rate were determined. The pathological changes were observed with HE staining. The infiltration of NK cells in tumor tissues was observed with immunohistochemical method. The proportions of NK cells in the liver and spleen were assessed with flow cytometry. The mRNA expressions of perforin and granzyme B in tumor tissues were detected with real-time PCR. Results Compared with the model group, the other groups had significantly lower/smaller tumor volume and weight(P<0.05)and more obvious necrosis. The infiltration of NK cells increased in the TSPG group(P<0.05). The proportions of NK cells in the liver and spleen, and the mRNA expressions of perforin and Granzyme B increased in the TSPG group and TSPG+5-Fu group(P<0.05). Conclusion TSPG promotes the antitumor effects of 5-Fu, which may be explained by the increased number of NK cells and cytotoxity.

Key words: Total saponins of Panax ginseng, 5-fluorouracil, Orthotopic liver transplantation tumor, NK cell

CLC Number: 

  • R574
[1] Usmani A, Mishra A, Ahmad M. Nanomedicines: a theranostic approach for hepatocellular carcinoma[J]. Artif Cells Nanomed Biotechnol, 2018, 46(4): 680-690.
[2] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[3] Kumral A, Giris M, Soluk-Tekkes, et al. Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats[J]. Pathophysiology, 2015, 22(2): 117-123.
[4] Ren M, Ye L, Hao X, et al. Polysaccharides from tricholoma matsutakeand lentinus edodes enhance 5-fluorouracilmediated H22 cell growth inhibition[J]. Tradit Chin Med, 2014, 34(3): 309-316.
[5] 康安, 钱静, 单进军, 等. 人参总皂苷主要成分大鼠体内药动学研究[J]. 中草药, 2015, 46(20): 3045-3050. KANG An, QIAN Jing, SHAN Jinjun, et al. In vivo pharmacokinetic study on total saponins from roots of Panax ginseng in rats[J]. Chinese Traditional and Herbal Drugs, 2015, 46(20): 3045-3050.
[6] 罗林明, 石雅宁, 姜懿纳, 等. 人参抗肿瘤作用的有效成分及其机制研究进展[J]. 中草药, 2017, 48(3): 582-596. LUO Linming, SHI Yaning, JIANG Yina, et al. Advance in components with antitumor effect of Panax ginseng and their mechanisms[J]. Chinese Traditional and Herbal Drugs, 2017, 48(3): 582-596.
[7] 贾执瑛, 谢燮, 王晓艳, 等. 人参主要成分对大鼠免疫功能的比较研究[J]. 中国中药杂志, 2014, 39(17): 3363-3366.
[8] Jia H, Zhao T, Zou D, et al. Therapeutic injection of a C-Type CpG ODN induced an antitumor immune response in C57/BL6 mice of orthotopically transplanted hepatocellular carcinoma[J]. Oncol Res, 2016, 23(6): 321-326.
[9] Cai L, Zhang Z, Zhou L, et al. Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients[J]. Clin Immunol, 2008, 129(3): 428-437.
[10] Chen H, Zhidan W, Xia R, et al. Scorpion venom activates natural killer cells in hepatocellular carcinoma via the NKG2D-MICA pathway[J]. Int Immunopharmacology, 2016, 35: 307-314. doi: 10.1016/j.intimp.2016.03.045.
[11] Ke M, Wang H, Zhou Y, et al. SEP enhanced the antitumor activity of 5-fluorouracil by up-regulating NKG2D/MICA and reversed immune suppression via inhibiting ROS and caspase-3 in mice[J]. Oncotarget, 2016, 7(31): 49509-49526.
[12] 周娅红. 人参总皂苷对免疫低下小鼠免疫功能的影响[J]. 中国中医急症, 2010, 19(9): 1559-1561.
[13] Shim JY, Kim H, Kim HD, et al. Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response[J]. Toxicol Appl harm, 2010, 242(3): 318-325.
[14] Sung SY, Hsieh CL, Wu D, et al. Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance[J]. Curr Probl Cancer, 2007, 31(2): 36-100.
[15] 姚蓉蓉, 王艳红. 肝细胞肝癌免疫微环境的研究进展[J]. 中国临床医学, 2014, 1(4): 487-497.
[16] Tosello-Trampont A, Surette FA, Ewald SE, et al. Immunoregulatory role of NK cells in tissue inflammation and regeneration[J]. Front Immunol, 2017, 20(8): 301-310.
[17] Marquardt N, Béziat V, Nyström S, et al. Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells[J]. J Immunol, 2015, 194(6): 2467-2471.
[18] Sojka DK1, Plougastel-Douglas B, Yang L, et al. Tissue-resident natural killer(NK)cells are cell lineages distinct from thymic and conventional splenic NK cells[J]. Elife, 2014, 3: e01659. doi: 10.7554/eLife.01659.
[19] Woodsworth DJ, Dreolini L, Abraham L, et al. Targeted cell-to-cell delivery of protein payloads via the granzyme-perforin pathway[J]. Mol Ther Methods Clin Dev, 2017, 7: 132-145. doi: 10.1016/j.omtm.2017.10.003.
[20] Li Q, Kobayashi M, Kawada T, et al. Effect of ziram on natural killer, lymphokine-activated killer, and cytotoxic T lymphocyte activity[J]. Archives of Toxicology 2012, 86(3): 475-481.
[21] Li Q, Kobayashi M, Inagaki H, et al. A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects[J]. J Biol Regul Homeost Agents, 2010, 24(2): 157-165.
[22] 曹雪涛, 高福, 龚非力, 等. 免疫学前沿. [M]. 3版. 北京: 人民卫生出版社, 2014: 82.
[23] Zhou Z, Yu X, Zhang J, et al. TLR7/8 agonists promote NK-DC cross-talk to enhance NK cell anti-tumor effects in hepatocellular carcinoma[J]. Cancer Lett, 2015, 369(2): 298-306.
[24] Nguyen-Pham TN, Yang DH, Nguyen TA, et al. Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy[J]. Cell Mol Immunol, 2012, 9(1): 45-53.
[25] Gao J, Duan Z, Zhang L, et al. Failure recovery of circulating NKG2D+CD56dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence[J]. Oncoimmunology, 2016, 5(1): e1048061. eCollection 2016.
[26] Sun C, Sun HY, Xiao WH, et al. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy[J]. Acta Pharmacol Sin, 2015, 36(10): 1191-1199.
[1] LI Tao, YANG Chunlin, DU Tong, LI Heng, WANG Congcong, LI Xiaoli, DUAN Ruisheng,ZHANG Peng. Effects of diabetes mellitus on the subsets and function of NK cells in myasthenia gravis [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 31-36.
[2] Jing SHAN,Xiaoqiu WANG,Dajin LI. Molecular mechanisms of NK cells involved in endometriosis and its associated infertility [J]. Journal of Shandong University (Health Sciences), 2021, 59(8): 8-13.
[3] LI Xiangqing, YIN Xin, ZHAO Xuelian, ZHAO Peiqing. Expression and clinical significance of circulating CD56bright subset of NK cells in patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 34-40.
[4] WANG Yao, CHEN Yan-hong, CHEN Hong. Correlation between sensibility, and side effects of 5-FU and DPYD gene polymorphisms in periphrel blood of patients with colon cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(S1): 18-21.
[5] CHU Qian-qian1, XU Gang2, REN Gui-jie1, XU Xia1, HU Zhong-yi1, LIU Yong-qing1, YUAN Hui-qing1, TIAN Ke-li1. Effect of rosiglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, in sensitizing 5-fluorouracil chemotherapy for colon cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(1): 66-71.
[6] LI Yu-sheng, HUANG Li, L Qi-jun, YU Yong-qin. Effect of interferon α-2b combined with 5-fluorouracil on the biological behavior of hepatoma cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(9): 48-.
[7] LIANG Xu-yang, CHENG Bao-quan, JIA Jun-ying, WANG Xu, REN Hong-bo. Inhibitory effect of ethyl pyruvate on the human  pancreatic carcinoma cell line [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(5): 48-53.
[8] HUANG Xianliang1, DONG Baihua1, HU Weixu2, WANG Qingjie2, SONG Bingfeng2, WANG Chune2,LIU Jia2, KONG Beihua1, QU Xun2. Exprlssions of CD49d and CD11b on CD56brightCD16- NK cell of early pregnancy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(5): 97-100.
[9] ZHANG Dong1, LI Cui-jing2, LI Lin-jun1, XI Yan-wei1, HUANG Gui-hua1. Colon-specific drug release from pH- and time-based pellets of  5-fluorouracil in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(12): 46-50.
[10] YANG Qing-rui,ZHANG Yuan-chao,LI Ming,SUN Hong-sheng,MU Kun. Role of 1-Hexylcarbamoyl-5-Fluorouracil on the Th1/Th2 balance in patients with ankylosing spondylitis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(1): 31-34.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd