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法夏苷通过抑制 TLR4/STAT3 信号通路抑制卵巢癌细胞的增殖、迁移和侵袭。

Fraxetin suppresses the proliferation, migration, and invasion of ovarian cancer cells by inhibiting the TLR4/STAT3 signaling pathway.

机构信息

Department of Traditional Chinese Medicine, Taizhou First People's Hospital, Taizhou City, China.

Department of Rehabilitation, Taizhou First People's Hospital, Taizhou City, China.

出版信息

Immunopharmacol Immunotoxicol. 2023 Jun;45(3):287-294. doi: 10.1080/08923973.2022.2141643. Epub 2022 Nov 8.

DOI:10.1080/08923973.2022.2141643
PMID:36346016
Abstract

BACKGROUND

Little therapeutic effect can be exerted on malignant ovarian cancer at the terminal period. Traditional Chinese medicine (TCM) has been a potential way for the treatment of various diseases. In this research, we probed into the potential curative effect of Fraxetin (FXT), a TCM monomer, on ovarian cancer.

METHODS

Ovarian cancer cells were treated with FXT at different concentrations for 12 h, or pretreated by 0.5 μM of colivelin, a STAT3 activator, for 1 h and then treated with 80 μM of FXT for 12 h. The viability of ovarian cancer cells was measured by MTT assay, and the cell colony number was counted after colony formation assay. Transwell assay was conducted for investigating the relationship between the FXT at different concentrations and the invasion as well as migration rates of ovarian cancer cells. The expressions of epithelial-to-mesenchymal transition (EMT)-associated markers and TLR4/STAT3 signaling pathway-related proteins in ovarian cancer cells after the treatment of FXT were measured by western blot.

RESULTS

FXT inhibited the viability, invasion, migration, and proliferation of SKOV3 and SW626 cells and suppressed EMT, but colivelin reversed the impacts of FXT. FXT also suppressed the expressions of N-cadherin, snail, vimentin, TLR4, phosphorylated (P)-STAT3, cyclin D1, and C-myc, whilst promoting that of E-cadherin by inhibiting the activation of TLR4/STAT3 signaling pathway.

CONCLUSION

FXT exerts a therapeutic effect on ovarian cancer by repressing the TLR4/STAT3 signaling pathway. With the accumulating concentrations of FXT, the therapeutic effect becomes more and more obvious.

摘要

背景

恶性卵巢癌晚期疗效甚微。中药(TCM)一直是治疗各种疾病的潜在方法。在这项研究中,我们探讨了 Fraxetin(FXT),一种 TCM 单体,对卵巢癌的潜在疗效。

方法

用不同浓度的 FXT 处理卵巢癌细胞 12 小时,或用 0.5μM 的 colivelin(一种 STAT3 激活剂)预处理 1 小时,然后用 80μM 的 FXT 处理 12 小时。用 MTT 法检测卵巢癌细胞活力,集落形成试验后计数细胞集落数。Transwell 试验用于研究不同浓度的 FXT 与卵巢癌细胞侵袭和迁移率之间的关系。用 Western blot 法检测 FXT 处理后卵巢癌细胞中上皮间质转化(EMT)相关标志物和 TLR4/STAT3 信号通路相关蛋白的表达。

结果

FXT 抑制 SKOV3 和 SW626 细胞的活力、侵袭、迁移和增殖,并抑制 EMT,但 colivelin 逆转了 FXT 的作用。FXT 还抑制了 N-钙粘蛋白、snail、波形蛋白、TLR4、磷酸化(P)-STAT3、细胞周期蛋白 D1 和 C-myc 的表达,同时通过抑制 TLR4/STAT3 信号通路的激活促进了 E-钙粘蛋白的表达。

结论

FXT 通过抑制 TLR4/STAT3 信号通路对卵巢癌发挥治疗作用。随着 FXT 浓度的增加,治疗效果越来越明显。

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