青蒿素衍生物通过抑制 TGF-β 信号通路在乳腺癌中失活肿瘤相关成纤维细胞。
Artemisinin derivatives inactivate cancer-associated fibroblasts through suppressing TGF-β signaling in breast cancer.
机构信息
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, 138 Xinlin Road, Nanjing, 210023, People's Republic of China.
出版信息
J Exp Clin Cancer Res. 2018 Nov 26;37(1):282. doi: 10.1186/s13046-018-0960-7.
BACKGROUND
Cancer-associated fibroblasts (CAFs) are activated fibroblasts associated with cancer. They have an important role in tumor growth and metastasis. Artemisinin (ART) is a sesquiterpene lactone extracted from Chinese herb qinghao, and artemether (ARM), artesunate (ARS) and dihydroartemisinin (DHA) were synthesized derivatives of artemisinin, which also have anti-malarial and anti-cancer effects such as artemisinin.
METHODS
In this study, we investigated the in-vitro and in-vivo effects of artemisinin derivatives on inactivating cancer-associated fibroblasts and uncovered its underlying mechanism.
RESULTS
We demonstrated that ARS and DHA could revert L-929-CAFs and CAFs from activated to inactivated state in vitro. Mechanically, ARS and DHA could suppress TGF-β signaling to inhibit activation of L-929-CAFs and CAFs, and decreased interaction between tumor and tumor microenvironment. The results showed that ARS and DHA could suppress CAFs-induced breast cancer growth and metastasis in the orthotopic model. Conformably, ARS and DHA suppressed TGF-β signaling to inactivate cancer-associated fibroblasts and inhibit cancer metastasis in vivo.
CONCLUSIONS
Artemisinin derivatives are potential therapeutic agents for the treatment of breast cancer.
背景
癌症相关成纤维细胞（CAFs）是与癌症相关的激活成纤维细胞。它们在肿瘤生长和转移中起着重要作用。青蒿素（ART）是从中药青蒿中提取的一种倍半萜内酯，而青蒿琥酯（ARM）、蒿甲醚（ARS）和双氢青蒿素（DHA）是青蒿素的合成衍生物，也具有抗疟和抗癌作用，如青蒿素。
方法
在这项研究中，我们研究了青蒿素衍生物对体外和体内失活癌症相关成纤维细胞的作用，并揭示了其潜在的机制。
结果
我们证明了 ARS 和 DHA 可以使体外的 L-929-CAFs 和 CAFs 从激活状态转变为失活状态。在机制上，ARS 和 DHA 可以抑制 TGF-β 信号通路，从而抑制 L-929-CAFs 和 CAFs 的激活，并减少肿瘤与肿瘤微环境之间的相互作用。结果表明，ARS 和 DHA 可以抑制 CAFs 诱导的乳腺癌在原位模型中的生长和转移。相应地，ARS 和 DHA 通过抑制 TGF-β 信号通路使癌症相关成纤维细胞失活，从而抑制体内癌症转移。
结论
青蒿素衍生物是治疗乳腺癌的潜在治疗剂。
Zotero 插件