Liujunzi decoction exerts potent antitumor activity in oesophageal squamous cell carcinoma by inhibiting miR-34a/STAT3/IL-6R feedback loop, and modifies antitumor immunity

体内 癌症研究 医学 车站3 免疫系统 佐剂 CD8型 细胞毒性T细胞 药理学 体外 单克隆抗体 抗体 外周血单个核细胞 免疫学 生物 细胞凋亡 生物技术 生物化学
作者
Yicun Han,Xiuqi Fan,Liyan Fan,Yaosong Wu,Zhexu Zhou,Ge Wang,Lanwei Guo,Weiqi Gao,Yulong Chen,Qilong Gao
出处
期刊:Phytomedicine [Elsevier]
卷期号:111: 154672-154672 被引量:3
标识
DOI:10.1016/j.phymed.2023.154672
摘要

Liujunzi decoction (LJZD), a traditional herbal formula and one of the most commonly used adjuvant medications for the treatment of oesophageal squamous cell carcinoma (ESCC), exerts good antitumor and immunomodulatory activity. However, its specific mechanism of action remains largely unclear.In order to examine the potential primary and adjuvant antitumor mechanisms of LJZD, both in vitro and in vivo.IL-6 and miR-34a inhibitors were used to activate the miR-34a/STAT3/IL-6R feedback loop to observe the effects of LJZD. A humanised mouse model with a functional human immune system was constructed to evaluate the antitumor efficacy of LJZD in vivo on xenograft tumours, which was compared to that of the positive control drug anti-PD-1 monoclonal antibodies (mAb). Finally, a co-culture system of peripheral blood mononuclear and tumour cells in vitro was used to analyse the cytotoxic activity of LJZD on T cells.LJZD significantly interfered with IL-6-induced activation of the miR-34a/STAT3/IL-6R feedback loop in ESCC by restoring the expression of the tumour suppressor miR-34a, and inhibited the proliferation of EC109 oesophageal cancer cells in a dose-dependant manner. Furthermore, LJZD effectively suppressed oesophageal tumour growth in vivo and alleviated organ injury and visceral index. Furthermore, LJZD boosted antitumor immunity by increasing IFN-γ expression and CD8+tumour-infiltrating lymphocytes (TILs) infiltration in the peripheral blood and tumour tissues, respectively, which may be related to a decrease in PD-1, but not PD-L1 expression. Finally, we confirmed that LJZD strengthens the killing ability of T cells by suppressing PD-1 expression in a co-culture system in vitro.LJZD exerts excellent antitumor effect by interfering with the miR-34a/STAT3/IL-6R feedback loop and augmenting antitumor immune responses. Which provides new insights into mechanisms for LJZD and sheds light on the multifaceted role of phytomedicine in cancer.
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