研究动态
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Obovatol 通过调节 JAK/STST3/PD-L1 通路抑制肝细胞癌细胞的增殖、侵袭和免疫逃逸。

Obovatol inhibits proliferation, invasion and immune escape of hepatocellular carcinoma cells through modulating the JAK/STST3/PD-L1 pathway.

发表日期:2024 Aug 14
作者: Chunhong Liao, Min Zhao, Xiao Jiang, Wei Sun, Qihong Zeng, Chengzhi Cai, Xinmin Yin
来源: INTERNATIONAL IMMUNOPHARMACOLOGY

摘要:

肝细胞癌(HCC)是一种常见的致命癌症,预后不佳。 Obovatol (Ob) 是一种从木兰叶和茎皮中提取的新型木脂素,对多种肿瘤表现出抗肿瘤作用。但其对HCC的作用和机制还有待进一步探讨。Huh7和Hep3B细胞以及BALB/c裸鼠通过细胞计数试剂盒8测定Ob对生长、侵袭和免疫逃逸的功能和机制、transwell、酶联免疫吸附测定 (ELISA) 和蛋白质印迹实验。Ob 降低 Huh7 和 Hep3B 细胞的细胞活力,IC50 值分别为 57.41 µM 和 62.86 µM。 Ob降低了Hep3B和Huh7细胞的侵袭能力、N-cadherin蛋白表达以及IL-10和TGF-β浓度,而升高了E-cadherin表达以及IFN-γ和IL-2含量。从机械角度来看,Ob 降低了 p-JAK/JAK、p-STAT3/STAT3 和 PD-L1 的蛋白水平,而用 JAK/STAT3 轴激活剂 RO8191 治疗后,该水平部分恢复。 Ob对Hep3B和Huh7细胞活力、侵袭能力、N-cadherin和E-cadherin蛋白水平以及IL-10、TGF-β、IFN-γ和IL-2浓度的影响RO8191 的管理逆转了这一情况。在体内,Ob 减少了肿瘤体积和重量,降低了 N-钙粘蛋白、PD-L1、p-JAK/JAK 和 p-STAT3/STAT3 的水平,并升高了 E-钙粘蛋白和 IFN-γ 的表达。Ob 下调了JAK/STST3/PD-L1 通路可减弱 HCC 的生长、侵袭和免疫逃逸。版权所有 © 2024 Elsevier B.V. 保留所有权利。
Hepatocellular carcinoma (HCC) is a common cancer that is fatal and has a dismal prognosis. Obovatol (Ob), a novel lignan derived from the leaf and stem bark of Magnolia obovata Thunb, has exhibited anti-tumor effect on diverse tumors. However, its effect and mechanisms on HCC remain to be further explored.Huh7 and Hep3B cells, as well as BALB/c nude mice were used to determine the function and mechanisms of Ob on growth, invasion and immune escape by cell counting kit-8, transwell, enzyme-linked immunosorbent assay (ELISA) and western blot experiments.Ob reduced the cell viability of Huh7 and Hep3B cells, with a IC50 value of 57.41 µM and 62.86 µM, respectively. Ob declined the invasion ability, the protein expression of N-cadherin and the concentrations of IL-10 and TGF-β, whereas increased the E-cadherin expression and the contents of IFN-γ and IL-2 in Hep3B and Huh7 cells. Mechanically, Ob decreased the protein level of p-JAK/JAK, p-STAT3/STAT3 and PD-L1, which was partly restored with the treatment of RO8191, an activator of JAK/STAT3 axis. The effect of Ob on the cell viability, the invasion ability, the protein level of N-cadherin and E-cadherin, and the concentrations of IL-10, TGF-β, IFN-γ and IL-2 in both Hep3B and Huh7 cells was reversed with the management of RO8191. In vivo, Ob reduced tumor volume and weight, the level of N-cadherin, PD-L1, p-JAK/JAK, and p-STAT3/STAT3, with an elevated expression of E-cadherin and IFN-γ.Ob downregulated the JAK/STST3/PD-L1 pathway to attenuate the growth, invasion and immune escape of HCC.Copyright © 2024 Elsevier B.V. All rights reserved.