Dihydroartemisinin induces apoptosis and inhibits proliferation, migration, and invasion in epithelial ovarian cancer via inhibition of the hedgehog signaling pathway.
Dihydroartemisinin induces apoptosis and inhibits proliferation, migration, and invasion in epithelial ovarian cancer via inhibition of the hedgehog signaling pathway.
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DOI：
10.1002/cam4.1827
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发表时间：
2018-11
期刊：
影响因子：
4
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Liu Y;Gao S;Zhu J;Zheng Y;Zhang H;Sun H
双氢青蒿素（DHA）是从传统中药青蒿中提取的青蒿素的主要成分，长期以来一直用于疟疾的治疗。最近，许多研究表明，除了抗疟疾作用外，DHA还对某些类型的肿瘤（包括卵巢癌）具有抗癌活性。然而，DHA抗卵巢癌的确切机制仍不清楚。Hedgehog（Hh）通路的异常激活与卵巢癌的发生、发展密切相关。我们进行这项研究，以阐明DHA对卵巢癌细胞的生物学行为的影响，并确定其对Hh信号通路的影响。CCK 8测定和流式细胞术用于评估DHA对卵巢癌细胞和HOSEPIC（人卵巢表面上皮细胞）中响应DHA处理的细胞活力和凋亡的影响。采用Transwell膜小室分析DHA对卵巢癌细胞迁移和侵袭的影响。通过RT-qPCR和Western印迹分析DHA对Hh信号传导的影响。DHA在体外能显著抑制卵巢癌细胞的增殖、迁移和侵袭，并诱导细胞凋亡。相比之下，DHA对HOSEPIC中的细胞增殖和凋亡几乎没有影响。DHA抑制hedgehog信号通路。此外，DHA还能抑制Purmorphamine（Hh信号通路激动剂）诱导的细胞增殖、细胞迁移和细胞侵袭，并抑制细胞凋亡。重要的是，DHA增强了GANT 61（hedgehog信号通路抑制剂）诱导的细胞凋亡以及对细胞活力、迁移能力和侵袭能力的抑制。这项研究表明，DHA抑制细胞活力，迁移和侵袭，以及诱导细胞凋亡上皮性卵巢癌通过抑制Hh信号通路。
Dihydroartemisinin (DHA), the primary of artemisinin extracted from the traditional Chinese medicine Artemisia annua, has been used in malaria treatment for a long time. Recently, many studies have indicated that, in addition to antimalarial effects, DHA also exhibits anticancer activity in certain types of neoplasms, including ovarian cancer. However, the precise anti‐ovarian cancer mechanism of DHA is still unclear. Abnormal activation of the hedgehog (Hh) pathway is closely related to tumorigenesis and progression of ovarian cancer. We performed this study to elucidate the effects of DHA on the biological behavior of ovarian cancer cells and to determine its effects on the Hh signaling pathway. CCK8 assays and flow cytometry were used to evaluate the effects of DHA on cell viability and apoptosis in both ovarian cancer cells and HOSEPICs (human ovarian surface epithelial cells) in response to DHA treatment. Transwell membrane chambers were used to analyze the effects of DHA on the migration and invasion of epithelial ovarian cancer cells following treatment with DHA. The impact of DHA on Hh signaling was analyzed by RT‐qPCR and Western blot. DHA significantly inhibited proliferation, migration, and invasion of ovarian cancer cells, and induced apoptosis in vitro. In contrast, DHA had few effects on cell proliferation and apoptosis in HOSEPICs. DHA inhibited the hedgehog signaling pathway. Furthermore, DHA inhibited purmorphamine (Hh signaling pathway agonist)‐induced cell proliferation, cell migration, and cell invasion and the inhibition of apoptosis. Importantly, DHA enhanced GANT61 (hedgehog signaling pathway inhibitor)‐induced apoptosis and the inhibition of cell viability, migratory capacity, and invasive ability. This study demonstrates that DHA inhibits cell viability, migration, and invasion, as well as induces apoptosis in epithelial ovarian cancer through suppression of the Hh signaling pathway.
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影响因子：
--
作者：
Fu X;Li Y;Alvero A;Li J;Wu Q;Xiao Q;Peng Y;Hu Y;Li X;Yan W;Guo K;Zhou W;Wang Y;Liu J;Zhang Y;Mor G;Wen J;Yin G
通讯作者：
Yin G
影响因子：
4.7
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Lai, H
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影响因子：
2
作者：
Wang, Zhenzhong;Wang, Chao;Wang, Shou-Lin
通讯作者：
Wang, Shou-Lin