异山羊草内酯通过抑制ERK信号通路抑制胆囊癌的进展。
Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway.
发表日期:2023 Dec
作者:
Xingyu Lv, Yuqi Lin, Xi Zhu, Xiujun Cai
来源:
PHARMACEUTICAL BIOLOGY
摘要:
胆囊癌(GBC)是胆道最常见的恶性肿瘤。异芹内酯乳酮(IAL)是从合欢根 (Inula helenium L.) (菊科)中分离出的一种活性倍半萜内酯化合物,具有抗肿瘤作用。本研究探讨了IAL对GBC的影响。在体外实验中,使用IAL(0,10,20和40μM)处理NOZ和GBC-SD细胞24h。以DMSO处理的细胞为对照组。通过CCK-8实验,Transwell实验,流式细胞仪和Western blot来测量细胞增殖,迁移,侵入和凋亡。体内实验中,通过注射裸鼠(BALB / C)的5 x 10^6个NOZ细胞来建立皮下肿瘤异种移植模型。小鼠分为对照组(等量DMSO),IAL组(10 mg / kg / day)和IAL + Ro 67-7476组(IAL,10 mg / kg / day; Ro 67-7476,4 mg / kg / day)。研究持续时间为30天。与DMSO组相比,IAL 40μM组抑制了NOZ(IC50 15.98μM)和GBC-SD(IC50 20.22μM)的细胞增殖约70%。迁移和侵袭抑制约80%。细胞凋亡率增加约三倍。 ERK的磷酸化水平降低至30-35%。 体内IAL可抑制肿瘤体积和重量(约80%减少)。此外,在体内和体外,IAL的作用被Ro 67-7476废除。我们的研究结果表明,IAL可以通过抑制ERK信号通路来抑制体内外GBC的进展。
Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. Isoalantolactone (IAL), an active sesquiterpene lactone compound isolated from the roots of Inula helenium L. (Asteraceae), has antitumour effects.This study investigates the effects of IAL on GBC.In vitro, NOZ and GBC-SD cells were treated with IAL (0, 10, 20 and 40 μM) for 24 h. The DMSO-treated cells were selected as a control. Cell proliferation, migration, invasion and apoptosis were measured by the CCK-8 assay, transwell assay, flow cytometry and western blot. In vivo, subcutaneous tumour xenografts were constructed by injecting nude mice (BALB/C) with 5 × 106 NOZ cells. Mice were divided into the control group (equal amount of DMSO), the IAL group (10 mg/kg/day) and the IAL + Ro 67-7476 group (IAL, 10 mg/kg/day; Ro 67-7476, 4 mg/kg/day). The study duration was 30 days.Compared with the DMSO group, cell proliferation of NOZ (IC50 15.98 μM) and GBC-SD (IC50 20.22 μM) was inhibited by about 70% in the IAL 40 μM group. Migration and invasion were suppressed by about 80%. Cell apoptosis rate was increased about three-fold. The phosphorylation level of ERK was decreased to 30-35%. Tumour volume and weight (about 80% reduction) were suppressed by IAL in vivo. Moreover, the effects of IAL were abolished by Ro 67-7476 in vitro and in vivo.Our findings indicate that IAL could inhibit GBC progression in vitro and in vivo by inhibiting the ERK signalling pathway.