|Table of Contents|

Thymoquinone regulates cisplatin resistance of human lung adenocarcinoma A549/DDP cells byinducing ferroptosis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 21
Page:
4049-4053
Research Field:
Publishing date:

Info

Title:
Thymoquinone regulates cisplatin resistance of human lung adenocarcinoma A549/DDP cells byinducing ferroptosis
Author(s):
ZHANG Yujiao1; LIU Xizhi2; ZHAO Xinhan2
1.Department of Respiratory and Critical Care Medicine,the Second Affiliated Hospital of Xi’an Jiaotong University,Shaanxi Xi’an 713599,China;2.Department of Oncology,the First Affiliated Hospital of Xi’an Jiaotong University,Shaanxi Xi’an 710061,China.
Keywords:
lung adenocarcinoma cancer; thymoquinone; ferroptosis; cisplatin resistance
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.21.006
Abstract:
Objective:To investigate the effects of thymoquinone on the cisplatin resistance of human lung adenocarcinoma A549/DDP cells and its mechanism.Methods:A549/DDP cells were treated with different concentrations of TQ or cisplatin,and cell proliferation ability of cells was detected by CCK8 assay and colony forming assay.Cell apoptosis was observed flow cytometry.ROS levels in different group were determined by flow cytometry.Western blot was used to detect the ferroptosis related markers SLC7A11,GPX4 and ACSL4.Results:Thymoquinone inhibited the proliferation of A549/DDP cells in a dose- and time- dependent manner.Thymoquinone combined with cisplatin decreased the proliferation and increased the apoptosis significantly in A549/DDP cells,compared with cisplatin alone group.Thymoquinone combined with cisplatin increased ROS level,ACSL4 level,and decreased SLC7A11 as well as GPX4,which could be reversed by ferroptosis inhibitor Ferrostatin-1.Conclusion:Thymoquinone regulates cisplatin resistance of human lung adenocarcinoma A549/DDP cells through inducing ferroptosis.

References:

［1］SIEGEL RL,MILLER KD,WAGLE NS,et al.Cancer statistics,2023［J］.CA Cancer J Clin,2023,73(1):17-48.
［2］YANG H,GUO Q,WU J,et al.Deciphering the effects and mechanisms of Yi-Fei-San-Jie-pill on non-small cell lung cancer with integrating network target analysis and experimental validation［J］.Front Pharmacol,2022,13:851554.
［3］TFAYLI AH,SFEIR PM,YOUSSEF BY,et al.Locally advanced lung cancer［J］.CA Cancer J Clin,2021,71(6):461-465.
［4］MAHMOUD YK,ABDELRAZEK HMA.Cancer:thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy［J］.Biomed Pharmacother,2019,115:108783.
［5］MEKHEMAR M,HASSAN Y,DORFER C.Nigella sativa and thymoquinone:A natural blessing for periodontal therapy［J］.Antioxidants(Basel),2020,9(12):1260-1280.
［6］IMRAN M,RAUF A,KHAN IA,et al.Thymoquinone: A novel strategy to combat cancer:A review［J］.Biomed Pharmacother,2018,106:390-402.
［7］CHEN LY,LI XX,LIU LB,et al.Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-gamma-lyasefunction［J］.Oncol Rep,2015,33(3):1465-1474.
［8］YAMAGUCHI H,HSU JL,CHEN CT,et al.Caspase -independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells［J］.Clin Cancer Res,2013,19(4):845-854.
［9］王睿，沙仁高娃.顺铂诱导铁死亡促进肿瘤相关巨噬细胞极化抑制宫颈癌细胞耐药性［J］.现代肿瘤医学，2022,30（13）:2320-2325.WANG R,Sharengaowa.Cisplatin-induced ferroptosis promotes tumor-associated macrophage polarization to inhibits drug resistance in cervical cancer cells［J］.Modern Oncology，2022,30（13）:2320-2325.
［10］AKERFELDT MC,TRANC M,SHEN C,et al.Interactions of cisplatin and the copper transporter CTR1 in human colon cancer cells［J］.J Biol Inorg Chem,2017,22(5):765-774.
［11］ROOSW P,KAINA B.DNA damage-induced cell death:from specific DNA lesions to the DNA damage response and apoptosis［J］.Cancer Lett,2013,332(2):237-248.
［12］WANG D,LIPPARD SJ.Cellular processing of platinum anticancer drugs［J］.Nat Rev Drug Discov,2005,4(4):307-320.
［13］RABBANI N,THORNALLEY PJ.Dicarbonyl proteome and genome damage in metabolic and vascular disease［J］.Biochem Soc Trans,2014,42(2):425-432.
［14］SULLIVAN LB,GUI DY,VANDER MG.Altered metabolite levels in cancer:implications for tumour biology and cancer therapy［J］.Nat Rev Cancer,2016,16(11):680-693.
［15］王爽，荣雪竹，王斯，等.PAK2通过调节ERK信号通路的活性促进肺癌细胞顺铂耐药［J］.现代肿瘤医学，2023,31（13）：2448-2454.WANG S,RONG XZ,WANG S,et al.PAK2 promotes cisplatin resistance in lung cancer cells by regulating the activity of ERK signaling pathway［J］.Modern Oncology，2023,31（13）：2448-2454.
［16］BALLOUT F, HABLI Z,RAHAL ON,et al.Thymoquinone-based nanotechnology for cancer therapy:promises and challenges［J］.Drug Discov Today,2018,23(5):1089-1098.
［17］SIEGEL RL,MILLER KD,JEMAL A.Cancer statistics,2020［J］.CA Cancer J Clin,2020,70(1):7-30.
［18］FORCINA GC，DIXON SJ.GPX4 at the crossroads of lipid homeostasis and ferroptosis［J］.Proteomics,2019,19(18):e1800311.
［19］DOLL S,PRONETH B,TYURINA YY,et al.ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition［J］.Nat Chem Biol,2017,13(1):91-98.
［20］LAGROST L,MASSON D.The expanding role of lyso-phosphatidylcholine acyltransferase-3(LPCAT3),a phospholipid-remodeling enzyme,in health and disease［J］.Curr Opin Lipidol,2022,33(3):193-198.
［21］程峰,张庸,王祥,等.谷胱甘肽过氧化物酶GPX4在铁死亡中的作用与机制研究进展［J］.现代肿瘤医学，2021,29(07):1254-1258.CHENG F,ZHANG Y,WANG X,et al.Research progress on the role and mechanism of GPX4 in ferroptosis［J］.Modern Oncology,2021,29(07):1254-1258.

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Last Update: 2024-09-30