Study on the mechanism of 17-Hydroxy-jolkinolide B on anaplastic thyroid cancer cell.

Lei Yang, Wanying Shi, Dihua Li, Yiming Shen, Ning Li, Zhaowei Meng
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Abstract

Background: Anaplastic thyroid cancer (ATC) has a dismal prognosis, and the optimal treatment has not yet been confirmed. Euphorbia fischeriana Steud has been proven to exhibit pharmacological properties, including various antitumor effects, that can be used to treat numerous diseases and has been used to treat cancer. 17-Hydroxy-jolkinolide B (17-HJB) is one of the major diterpenoids produced from plants, but little research has investigated how it affects cancer.

Methods: MTT assays, glucose and lactate concentration detection, Annexin V-FITC detection via cytometry, and Western blotting were performed to research the mechanism of 17-HJB.

Results: Cell viability was inhibited in a concentration-dependent manner after 17-HJB treatment. 17-HJB inhibited glucose consumption and lactate production, and the expression of the glucose transporter GLUT1 and proteins associated with glycolysis, HK2, PFK1, and PKM2, was significantly downregulated. 17-HJB induced apoptosis, and the expression of signaling proteins related to apoptosis, such as Caspase-3 and cleaved Caspase-3, was upregulated. In vivo, 17-HJB effectively inhibited the growth of ATC tumors. The results of the expression of glycolysis-related enzyme proteins and apoptosis signaling proteins were consistent with those in vitro.

Conclusions: 17-HJB inhibited the growth of ATCs both in vivo and in vitro. The mechanism may be related to the effects on glucose metabolism and the inhibition of aerobic glycolysis. 17-HJB also induced ATC apoptosis.

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17-Hydroxy-jolkinolide B 对无性甲状腺癌细胞作用机制的研究
背景:甲状腺无节细胞癌(ATC)的预后很差,最佳治疗方法尚未确定。大戟科植物 Steud 已被证实具有药理特性,包括各种抗肿瘤作用,可用于治疗多种疾病,并已被用于治疗癌症。17-Hydroxy-jolkinolide B(17-HJB)是植物中产生的主要二萜类化合物之一,但很少有人研究它如何影响癌症:方法:通过 MTT 试验、葡萄糖和乳酸盐浓度检测、细胞计数法检测 Annexin V-FITC 以及 Western 印迹法研究 17-HJB 的作用机制:结果:细胞活力在 17-HJB 处理后受到抑制,且呈浓度依赖性。结果:17-HJB 可抑制葡萄糖消耗和乳酸生成,葡萄糖转运体 GLUT1 和糖酵解相关蛋白 HK2、PFK1、PKM2 的表达显著下调。17-HJB 可诱导细胞凋亡,与细胞凋亡相关的信号蛋白如 Caspase-3 和裂解 Caspase-3 的表达上调。在体内,17-HJB 能有效抑制 ATC 肿瘤的生长。糖酵解相关酶蛋白和凋亡信号蛋白的表达结果与体外实验结果一致:结论:17-HJB在体内和体外均能抑制ATC的生长。结论:17-HJB 可抑制 ATC 在体内和体外的生长,其机制可能与影响葡萄糖代谢和抑制有氧糖酵解有关。17-HJB 还能诱导 ATC 细胞凋亡。
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