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小豆蔻明通过调节FOXO3a-FOXM1轴促进胰腺癌的凋亡及对吉西他滨的化疗敏感性。

Cardamonin Promotes the Apoptosis and Chemotherapy Sensitivity to Gemcitabine of Pancreatic Cancer Through Modulating the FOXO3a-FOXM1 Axis.

作者信息

Sun Huapeng, Zhang Na, Jin Yiqiang, Xu Haisheng

机构信息

Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.

Department of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.

出版信息

Dose Response. 2021 Dec 21;19(4):15593258211042163. doi: 10.1177/15593258211042163. eCollection 2021 Oct-Dec.

DOI:10.1177/15593258211042163
PMID:34987330
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8725235/
Abstract

Cardamonin (CAR), a flavone existing in the Alpinia plant, has been found to modulate multiple biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects. Nevertheless, the influence of CAR on pancreatic cancer (PC) is less understood. Here, we conducted and experiments to explore the functions of CAR on PC cells' proliferation, apoptosis and chemosensitivity to gemcitabine (GEM). The growth of PC cells (including PANC-1 and SW1990) was evaluated by the cell counting kit-8 assay, colony formation assay and xenograft tumor experiment. Besides, the apoptosis was determined by flow cytometry and western blot (WB). Moreover, the FOXO3a-FOXM1 pathway expression was tested by reverse transcription-polymerase chain reaction and WB. Our data suggested that CAR restrained cell proliferation, growth and expedited apoptosis both and . Moreover, CAR sensitized PC cells to GEM. Mechanistically, CAR heightened FOXO3a while repressed FOXM1. Further loss-of-function assays revealed that down-regulating FOXO3a markedly dampened the anti-tumor effect induced by CAR and accelerated the FOXM1 expression. Our data confirmed that CAR exerted an anti-tumor function in PC dependently by modulating the FOXO3a-FOXM1 axis.

摘要

小豆蔻明(CAR)是一种存在于山姜属植物中的黄酮,已发现它能调节多种生物学活性,包括抗氧化、抗炎和抗肿瘤作用。然而,CAR对胰腺癌(PC)的影响尚不清楚。在此,我们进行了[具体实验1]和[具体实验2]实验,以探究CAR对PC细胞增殖、凋亡及对吉西他滨(GEM)化疗敏感性的作用。通过细胞计数试剂盒-8法、集落形成实验和异种移植肿瘤实验评估PC细胞(包括PANC-1和SW1990)的生长情况。此外,通过流式细胞术和蛋白质免疫印迹(WB)检测细胞凋亡情况。而且,通过逆转录-聚合酶链反应和WB检测FOXO3a-FOXM1通路的表达。我们的数据表明,CAR在体内和体外均抑制细胞增殖、生长并加速细胞凋亡。此外,CAR使PC细胞对GEM敏感。机制上,CAR上调FOXO3a同时下调FOXM1。进一步的功能缺失实验表明,下调FOXO3a显著减弱了CAR诱导的抗肿瘤作用并加速了FOXM1的表达。我们的数据证实,CAR通过调节FOXO3a-FOXM1轴在PC中发挥抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/c6b39f1a39e9/10.1177_15593258211042163-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/3c788c9be9a7/10.1177_15593258211042163-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/4515fb1aa6f7/10.1177_15593258211042163-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/844154ab3067/10.1177_15593258211042163-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/a7b0b6c42b3e/10.1177_15593258211042163-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/71c0dce68f46/10.1177_15593258211042163-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/c6b39f1a39e9/10.1177_15593258211042163-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/3c788c9be9a7/10.1177_15593258211042163-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/4515fb1aa6f7/10.1177_15593258211042163-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/844154ab3067/10.1177_15593258211042163-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/a7b0b6c42b3e/10.1177_15593258211042163-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/71c0dce68f46/10.1177_15593258211042163-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38bf/8725235/c6b39f1a39e9/10.1177_15593258211042163-fig6.jpg

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