A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer
文献类型：期刊论文
| 作者 | Wang, Yumeng1,2; Lu, Chong1,2; Huang, Haixia1,2; Yao, Sheng3 ; Xu, Congjian1,2; Ye, Yang3; Gui, Suiqi1,2; Li, Guiling1,2
|
| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
 |
| 出版日期 | 2021-03-01 |
| 卷号 | 267页码:10 |
| 关键词 | Cervical cancer Tumor-associated dendritic cell (TADC) Suppressor of cytokine signaling-1 (SOCS1) JAK/STAT pathway Immunotherapy Traditional Chinese medicine |
| ISSN号 | 0378-8741 |
| DOI | 10.1016/j.jep.2020.112837 |
| 通讯作者 | Li, Guiling(guilingli@fudan.edu.cn) |
| 英文摘要 | Ethnopharmacological relevance: 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. Aims: To explore the underlying mechanisms by which PE modulates tumor-associated dendritic cell (TADC) activation and function. Methods: 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. Results: 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. Conclusions: 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. |
| WOS关键词 | FATTY-ACIDS ; EXPRESSION ; STAT5 ; INNATE ; INHIBITION ; SUPPRESSORS ; MACROPHAGES ; NANOVACCINE ; MECHANISMS ; MATURATION |
| 资助项目 | National Natural Science Foundation of China[81873124] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000606373500005 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/295967]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Guiling |
| 作者单位 | 1.Fudan Univ, Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China 2.Fudan Univ, Obstet & Gynecol Hosp, Dept Integrat Western & Tradit Med, 128 Shen Yang Rd, Shanghai 200090, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yumeng,Lu, Chong,Huang, Haixia,et al. A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer[J]. JOURNAL OF ETHNOPHARMACOLOGY,2021,267:10. |
| APA | Wang, Yumeng.,Lu, Chong.,Huang, Haixia.,Yao, Sheng.,Xu, Congjian.,...&Li, Guiling.(2021).A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer.JOURNAL OF ETHNOPHARMACOLOGY,267,10. |
| MLA | Wang, Yumeng,et al."A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer".JOURNAL OF ETHNOPHARMACOLOGY 267(2021):10. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。