Effects of triggers of senescence and senolysis in murine pancreatic cancer cells

作     者：Denis Revskij Aline Woitas Bianca Kölle Camilla Umstätter Dietmar Zechner Faiz M Khan Georg Fuellen Robert Jaster Denis Revskij;Aline Woitas;Bianca Kölle;Camilla Umstätter;Dietmar Zechner;Faiz M Khan;Georg Fuellen;Robert Jaster

作者机构：Department of MedicineⅡDivision of GastroenterologyRostock University Medical CenterRostockGermany Rudolf-Zenker-Institute of Experimental SurgeryRostock University Medical CenterRostockGermany Department of Systems Biology and BioinformaticsInstitute of Computer ScienceUniversity of RostockRostockGermany Institute for Biostatistics and Informatics in Medicine and Ageing ResearchRostock University Medical CenterRostockGermany 

出 版 物：《Hepatobiliary & Pancreatic Diseases International》 (国际肝胆胰疾病杂志（英文版）)

年 卷 期：2024年第23卷第6期

页      面：628-637页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by a grant from the Bundesministerium fur Bildung und Forschung(01ZX1903A) 

主　　题：Pancreatic cancer Panc02 cells Etoposide Irradiation Navitoclax 

摘      要：Background:The combination of senescence triggers with senolytic drugs is considered a promising new approach to cancer ***,we studied the efficacy of the genotoxic agent etoposide(Eto)and irradiation in inducing senescence of Panc02 pancreatic cancer cells,and the capability of the Bcl-2 inhibitor navitoclax(ABT-263;Nav)to trigger ***:Panc02 cells were treated with Eto or irradiated with 5–20 Gy before exposure to *** survival,proliferation,and senescence were assessed by trypan blue staining,quantification of DNA synthesis,and staining of senescence-associatedβ-galactosidase(SA-β-Gal)-positive cells,*** of mRNA were determined by real-time polymerase chain reaction,and protein expression was analyzed by ***02 cells were also grown as pancreatic tumors in mice,which were subsequently treated with Eto and ***:Eto and irradiation had an antiproliferative effect on Panc02 cells that was significantly or tendentially enhanced by *** vivo,Eto and Nav together,but not Eto alone,significantly reduced the proportion of proliferating *** expression of the senescence markerγH2AX and tumor infiltration with T-cells were not affected by the *** vitro,almost all Eto-exposed cells and a significant proportion of cells irradiated with 20 Gy were SA-β-*** of Nav reduced the percentage of SA-β-Gal-positive cells after irradiation but not after pretreatment with *** response to triggers of senescence,cultured Panc02 cells showed increased protein levels ofγH2AX and the autophagy marker LC3B-II,and higher mRNA levels of Cdkn1a,Mdm2,and PAI-1,while the effects of Nav were ***:In vitro and in vivo,the combination of senescence triggers with Nav inhibited tumor cell growth more effectively than the triggers *** data also provide some evidence for senolytic effects of Nav in vitro.