The Second School of Clinical Medicine, Southern Medical University, No.1023 South Shatai Road, Baiyun District, Guangzhou, 510515 Guangdong, China; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080 Guangdong, China; Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, NO.134, East Street, Fuzhou, 350001 Fujian, China.
Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, NO.134, East Street, Fuzhou, 350001 Fujian, China.
Biomed Pharmacother. 2020 Dec;132:110830. doi: 10.1016/j.biopha.2020.110830. Epub 2020 Oct 12.
This study aimed to examine eugenic acid (EA) as an alternative therapeutic approach against pancreatic cancer. The pancreatic cancer xenograft mouse model was employed to determine the impacts of treatment with EA on the growth of tumors. Expressions of NF-κB subunit RelA as well as Anterior gradient 2 (AGR2) were quantified in pancreatic cells treated with EA. Chromatin immunoprecipitation and luciferase report assay were performed to examine the regulation of AGR2 by RelA. The function of AGR2 as a downstream effector EA treatment was further assessed through overexpression of AGR2 in pancreatic cells. EA suppressed the growth of xenograft pancreatic tumor, and promoted the overall survival of animals with xenograft tumors. Furthermore, EA downregulated the expression of AGR2 in pancreatic cancer cells via the RelA binding site. Ectopic AGR2 overexpression attenuated the EA-elicited inhibition on the growth of xenograft pancreatic tumor, and negated the EA-induced enhancement of mouse survival. EA ameliorates pancreatic cancer through suppression of AGR2 expression, and future studies in clinical settings are needed to further assess the anti-cancer efficacy of EA.
本研究旨在探讨 Eugenol acid (EA) 作为一种治疗胰腺癌的替代方法。采用胰腺癌异种移植小鼠模型，研究了 EA 处理对肿瘤生长的影响。检测了经 EA 处理的胰腺细胞中 NF-κB 亚基 RelA 以及 Anterior gradient 2 (AGR2) 的表达情况。通过染色质免疫沉淀和荧光素酶报告基因检测实验，研究了 RelA 对 AGR2 的调控作用。通过在胰腺细胞中转染 AGR2 过表达载体，进一步评估了 AGR2 作为 EA 治疗下游效应物的功能。EA 抑制了异种移植胰腺肿瘤的生长，并提高了携带异种移植肿瘤动物的总生存率。此外，EA 通过 RelA 结合位点下调了胰腺癌细胞中 AGR2 的表达。过表达 AGR2 可减弱 EA 对异种移植胰腺肿瘤生长的抑制作用，并消除 EA 诱导的小鼠生存能力的增强。EA 通过抑制 AGR2 的表达改善胰腺癌，需要在临床环境中进一步评估 EA 的抗癌疗效。
