Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200090, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fudan University, Shanghai, 200011, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
J Ethnopharmacol. 2021 Mar 1;267:112837. doi: 10.1016/j.jep.2020.112837. Epub 2020 Apr 7.
Pinellia pedatisecta Schott extract (PE) is generated from Pinellia pedatisecta Schott, a traditional Chinese medicinal plant. PE suppresses cervical tumor growth and exhibits effects on dendritic cells (DCs) that lead to modulation of antitumor CD4 and CD8 responses.
To explore the underlying mechanisms by which PE modulates tumor-associated dendritic cell (TADC) activation and function.
DCs and TADCs were generated from murine bone marrow and exposed to PE solutions at different doses, as well as to repeated doses separated at different time intervals. Quantitative PCR, Western blot analysis, flow cytometry, and gene silencing were used to analyze the modulatory effects of PE on the SOCS1/JAK2/STAT pathways. Furthermore, we separated human cervical tumor-infiltrated DCs (TIDCs) and conducted an ex-vivo stimulation model to observe the effect of PE. For phenotypic analysis of cultured DCs and ex vivo human specimens, we used flow cytometry to detect the molecular markers associated with cell function.
In cultured TADCs and human cervical TIDCs, maturation- and functional markers (MHCII, CD80, CD83, CD86, and IL-12) were downregulated, whereas SOCS1 was upregulated. PE enhanced the expression of CD80, CD86, and IL-12 in cervical TIDCs, which induced increased expression of CD107a, GZMB, and perforin in CTLs, and furthermore induced apoptosis in a larger number of tumor cells. In cultured TADCs, PE downregulated SOCS1 expression and activated the phosphorylation of JAK2, STAT1, STAT4, and STAT5 in both dose- and time-dependent manners. The effects of PE upregulating MHCII, CD80, CD86, IL-12 on TADCs were blocked after SOCS1 silencing.
In this study, PE restored the impaired function of cervical TIDCs, thereby eliciting further antitumor CTL responses. The effects of PE on TADCs were mediated through inhibition of SOCS1 and activation of downstream JAK2-STAT1/STAT4/STAT5 pathways. PE may be a potent and effective immunomodulatory drug for antitumor treatment via the blockade of SOCS1 signaling in DCs.
半夏提取物（PE）源自半夏，是一种传统的中药。PE 抑制宫颈肿瘤生长，并对树突状细胞（DC）产生影响，从而调节抗肿瘤 CD4 和 CD8 反应。
探索 PE 调节肿瘤相关树突状细胞（TADC）激活和功能的潜在机制。
从鼠骨髓中生成 DC 和 TADCs，并将其暴露于不同剂量的 PE 溶液中，以及在不同时间间隔重复给药。采用定量 PCR、Western blot 分析、流式细胞术和基因沉默技术分析 PE 对 SOCS1/JAK2/STAT 通路的调节作用。此外，我们分离人宫颈肿瘤浸润性 DC（TIDC）并进行体外刺激模型观察 PE 的作用。对于培养的 DC 和体外人标本的表型分析，我们使用流式细胞术检测与细胞功能相关的分子标记物。
在培养的 TADCs 和人宫颈 TIDC 中，成熟和功能标记物（MHCII、CD80、CD83、CD86 和 IL-12）下调，而 SOCS1 上调。PE 增强了宫颈 TIDC 中 CD80、CD86 和 IL-12 的表达，诱导 CTL 中 CD107a、GZMB 和穿孔素的表达增加，并进一步诱导更多的肿瘤细胞凋亡。在培养的 TADCs 中，PE 下调 SOCS1 的表达，并以剂量和时间依赖性方式激活 JAK2、STAT1、STAT4 和 STAT5 的磷酸化。沉默 SOCS1 后，PE 上调 MHCII、CD80、CD86、IL-12 对 TADCs 的作用被阻断。
在这项研究中，PE 恢复了宫颈 TIDC 受损的功能，从而引发了进一步的抗肿瘤 CTL 反应。PE 对 TADCs 的作用是通过抑制 SOCS1 和激活下游 JAK2-STAT1/STAT4/STAT5 通路来介导的。PE 可能是一种有效的免疫调节药物，通过阻断 DC 中的 SOCS1 信号通路，用于抗肿瘤治疗。
