主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

JOURNAL OF BEIJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE ›› 2020, Vol. 43 ›› Issue (12): 1018-1026.doi: 10.3969/j.issn.1006-2157.2020.12.008

• Chinese Medicinal Pharmocology • Previous Articles     Next Articles

Mechanism of Qinma Fang inhibiting non-small cell lung cancer via regulating myeloid-derived suppressor cells*

Zhu Yangzhuangzhuang1, Hou Yifei1, Zhang Fei2, Jiao Xiaoning1, Su Lin1, Chen Xiao1, Zhu Shiguo1, Wei Luyao1, Wang Wantao1, Wang Jie1, Zhu Xiandan3, Zou Chunpu1, Xu Zihang1#   

  1. 1 School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
    2 Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;
    3 Science and Technology Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2020-06-11 Online:2020-12-30 Published:2021-01-05
  • Contact: Associate Prof. Xu Zihang, Ph. D.,Master's Supervisor. Shanghai University of Traditional Chinese Medicine. No.1200 Cailun Road, Pudong District, Shanghai 201203. E-mail: xuzihang_tcm@126.com
  • Supported by:
    National Natural Science Foundation for Young Scientists of China (No. 81804017), Shanghai Sailing Plan for Young Scientists (No. 18YF1423500), Postdoctoral Science Foundation of China (No. 2018M640416), Three-year Action Plan for Further Accelerating the Development of Traditional Chinese Medicine in Shanghai (2018-2020) (No. ZY (2018-2020)-CCCX-2001-01)

Abstract: Objective To investigate the antitumor effect of Qinma Fang (Scutellaria Root and Ephedra Herb Formula, QMF) on orthotopic lung cancer mice and explore its potential mechanism. Methods Mouse models of orthotopic lung cancer were established through intrapulmonary injection with LLC-luc cells. All mice were randomly divided into four groups: blank control group, cisplatin group (2 mg/kg cisplatin twice a week by intraperitoneal injection for 4 weeks), QMF group of high, medium, and low doses (QMF at 2.0, 1.0, and 0.5 g/kg once daily with intragastrical administration for 4 weeks). The general conditions of the mice (i.e. spirit, hair, activity, etc.) were observed and the survival length was recorded. MTT was used to detect the inhibitory effects on the proliferation of LLC-luc cells. Flow cytometry was used to detect the change in the numbers of MDSCs and T cells in the spleen and tumor of the model mice and assess the CD107α degranulation efficacy of CD8+, T cells. RT-PCR was applied to exeamine the Arg1, iNOS, STAT3 and STAT1 mRNA expressions in the mouse spleen. Western blot was performed to detecd the protein expressions of Arg1, STAT3 and pSTAT3 in mouse spleen. HE staining and ELISA were used to determine the liver and kidney toxicity of QMF. Results QMF at medium dose could significantly prolong the survival of tumor bearing mice (P<0.05). Intervention of QMF at different concentrations has no direct inhibitory effect on the proliferation of LLC-luc cells. However, QMF at medium dose significantly reduced the quantity of MDSCs (P<0.01) and increased the amount of T cells (especially CD8 +, T cells) (P<0.01) in the spleen and tumor of model mice. Meanwhile, the CD107α degranulation ability of CD8+, T cells was also remarkably enhanced (P<0. 01). In addition, the mRNA expressions of Arg1 and STAT3 related to the activation of MDSCs were obviously decreased after medium-dose QMF administration, and the protein levels of Arg1, STAT3 and pSTAT3 were also down-regulated accordingly (P<0.01). Moreover, no abnormalities were found in the pathological examination of liver and kidney tissue slides and the biochemical parameters. Conclusion QMF may inhibit the proliferation and activation of MDSCs by down-regulating the STAT3 signaling pathway, thus prolonging the survival of tumor-bearing mice with lung cancer. In addition, it is safe to use with minimal toxicity on kidney and liver. This study is conducive to the expansion of clinical application of QMF, and validate the argument that lung cancer might be induced by phlegm.

Key words: Qinma Fang, MDSCs, orthotopic lung cancer model, LLC-luc, phegm-polluted, mice

CLC Number: 

  • R285.5