Antibiotic tigecycline inhibits cell proliferation, migration and invasion via down‐regulating CCNE2 in pancreatic ductal adenocarcinoma

Yang, Jie; Dong, Zhen; Ren, Aishu; Fu, Gang; Zhang, Kui; Li, Changhong; Wang, Xiangwei; Cui, Hongjuan

doi:10.1111/jcmm.15086

Title: Antibiotic tigecycline inhibits cell proliferation, migration and invasion via down‐regulating CCNE2 in pancreatic ductal adenocarcinoma

Journal Article · Fri Mar 06 00:00:00 EST 2020 · Journal of Cellular and Molecular Medicine

DOI:https://doi.org/10.1111/jcmm.15086· OSTI ID:1603390

Yang, Jie ^[1];

^[1]; Ren, Aishu ^[2]; Fu, Gang ^[2]; Zhang, Kui ^[1]; Li, Changhong ^[1]; Wang, Xiangwei ^[3];

^[1]

State Key Laboratory of Silkworm Genome Biology Institute of Sericulture and Systems Biology Southwest University Beibei, Chongqing China, Cancer Center Medical Research Institute Southwest University Beibei, Chongqing China, Engineering Research Center for Cancer Biomedical and Translational Medicine Southwest University Beibei, Chongqing China, Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine Southwest University Beibei, Chongqing China
College of Stomatology Chongqing Medical University Chongqing China
Department of Urology Carson International Cancer Center Shenzhen University General Hospital &, Shenzhen University Clinical Medical Academy Center Shenzhen University Shenzhen China

Abstract Recently, many researches have reported that antibiotic tigecycline has significant effect on cancer treatment. However, biomedical functions and molecular mechanisms of tigecycline in human pancreatic ductal adenocarcinoma (PDAC) remain unclear. In the current study, we tried to assess the effect of tigecycline in PDAC cells. AsPC‐1 and HPAC cells were treated with indicated concentrations of tigecycline for indicated time, and then, MTT, BrdU and soft agar assay were used to test cell proliferation. The effect of tigecycline on cell cycle and cellular apoptosis was tested by cytometry. Migration and invasion were detected by wound healing assay and transwell migration/invasion assay. Expressions of cell cycle‐related and migration/invasion‐related protein were determined by using Western blot. The results revealed that tigecycline observably suppressed cell proliferation by inducing cell cycle arrest at G0/G1 phase and blocked cell migration/invasion via holding back the epithelial‐mesenchymal transition (EMT) process in PDAC. In addition, tigecycline also remarkably blocked tumorigenecity in vivo. Furthermore, the effects of tigecycline alone or combined with gemcitabine in vitro or on PDAC xenografts were also performed. The results showed that tigecycline enhanced the chemosensitivity of PDAC cells to gemcitabine. Interestingly, we found CCNE2 expression was declined distinctly after tigecycline treatment. Then, CCNE2 was overexpressed to rescue tigecycline‐induced effect. The results showed that CCNE2 overexpression significantly rescued tigecycline‐inhibited cell proliferation and migration/invasion. Collectively, we showed that tigecycline inhibits cell proliferation, migration and invasion via down‐regulating CCNE2, and tigecycline might be used as a potential drug for PDAC treatment alone or combined with gemcitabine.

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Sponsoring Organization:: USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research

Grant/Contract Number:: 2017YFC1308600; 2016YFC1302204; 81872071; 2019T120801; XDJK2019C013; XDJK2019C089

OSTI ID:: 1603390

Alternate ID(s):: OSTI ID: 1787147

Journal Information:: Journal of Cellular and Molecular Medicine, Journal Name: Journal of Cellular and Molecular Medicine Vol. 24 Journal Issue: 7; ISSN 1582-1838

Publisher:: Wiley-BlackwellCopyright Statement

Country of Publication:: Country unknown/Code not available

Language:: English

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Cited by: 15 works

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