Griseofulvin Radiosensitizes Non-Small Cell Lung Cancer Cells and Activates cGAS

作者全名："Wang, Xing; Raman, Natasha; Lemtiri-Chlieh, Ghali; Chang, Jinhee; Jagtap, Shreya; Chowdhury, Dipanwita Dutta; Ballew, Matthew; Carrieri, Francesca Anna; Nguyen, Triet; Nugent, Katriana; Peck, Travis; Levine, Michelle S.; Chan, Aaron; Lam, Christine; Malek, Reem; Hoang, Tung; Phillips, Ryan; Cheng, ZhuoAn; Taparra, Kekoa; Connis, Nick; Hann, Christine L.; Holland, Andrew; Tran, Phuoc T.; Lafargue, Audrey; Wang, Hailun"

作者地址："[Wang, Xing; Raman, Natasha; Lemtiri-Chlieh, Ghali; Chang, Jinhee; Jagtap, Shreya; Chowdhury, Dipanwita Dutta; Ballew, Matthew; Carrieri, Francesca Anna; Nguyen, Triet; Nugent, Katriana; Peck, Travis; Lam, Christine; Malek, Reem; Hoang, Tung; Phillips, Ryan; Cheng, ZhuoAn; Taparra, Kekoa; Wang, Hailun] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA; [Wang, Xing] Chongqing Med Univ, Affiliated Hosp 2, Dept Breast & Thyroid Surg, Chongqing, Peoples R China; [Chang, Jinhee; Jagtap, Shreya; Chowdhury, Dipanwita Dutta; Carrieri, Francesca Anna; Nguyen, Triet; Chan, Aaron; Tran, Phuoc T.; Lafargue, Audrey] Univ Maryland Baltimore, Sch Med, Dept Radiat Oncol, Div Translat Radiat Sci, Baltimore, MD 21201 USA; [Levine, Michelle S.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD USA; [Phillips, Ryan] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA; [Cheng, ZhuoAn] Shanghai Jiao Tong Univ, Renji Hosp, Sch Biomed Engn, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China; [Taparra, Kekoa] Stanford Med, Dept Radiat Oncol, Stanford, CA USA; [Connis, Nick; Hann, Christine L.; Holland, Andrew; Tran, Phuoc T.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Dept Oncol, Baltimore, MD USA; [Tran, Phuoc T.] Johns Hopkins Univ, James Buchanan Urol Inst, Sch Med, Dept Urol, Baltimore, MD USA; [Wang, Hailun] GenoImmune Therapeut, 388 Gaoxin 2nd Rd, Wuhan, Peoples R China; [Lafargue, Audrey] Univ Maryland Baltimore, Sch Med, 655 West Baltimore St,Bressler Res Bldg,Rm 8-020, Baltimore, MD 21201 USA"

通信作者："Wang, HL (通讯作者)，GenoImmune Therapeut, 388 Gaoxin 2nd Rd, Wuhan, Peoples R China.; Lafargue, A (通讯作者)，Univ Maryland Baltimore, Sch Med, 655 West Baltimore St,Bressler Res Bldg,Rm 8-020, Baltimore, MD 21201 USA."

来源：MOLECULAR CANCER THERAPEUTICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000973087300001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：22

期号：4

开始页：519

结束页：528

文献类型：Article

关键词：　

摘要："Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome approved treatment) inhibits CC, and combined with radiotherapy, resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiotherapy resulted in a significant tumor growth delay. Both GF and radiotherapy treat-ment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radio-resistant cells that was dependent on cGAS. In conclusion, GF increased radiotherapy efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiotherapy, and immunotherapy could be a promising strategy to treat NSCLC."

基金机构："Ride-Prostate Cancer Foundation; PCF-Movember Foundation-Distinguished Gentlemen's Ride-Prostate Cancer Foundation; NIH/NCI [U01CA212007, U01CA231776, U54CA273956]; DoD [W81XWH-21-1-0296, W81XWH-18-1-0435]; Uniting Against Lung Cancer Young Investigator Award; Johns Hopkins and Allegheny Health Network Award; Prostate Cancer Foundation (PCF); Radiological Society of North America; NIH [F31CA189588]"

基金资助正文："P.T. Tran was funded by an anonymous donor, PCF-Movember Foundation-Distinguished Gentlemen's Ride-Prostate Cancer Foundation and the NIH/NCI (U01CA212007, U01CA231776 and U54CA273956) and DoD (W81XWH-21-1-0296) . H. Wang is funded by a Uniting Against Lung Cancer Young Investigator Award and Johns Hopkins and Allegheny Health Network Award. A. Lafargue is funded by the DoD (W81XWH-18-1-0435) . R. Malek is funded by the Prostate Cancer Foundation (PCF) . R. Phillips is funded by the Radiological Society of North America. K. Taparra is funded by the NIH (F31CA189588) . The authors would like to acknowledge the SKCCC Experimental Irradiators Core at JHU (Esteban Velarde, M.S.) , the Irradiation Core at UMB-DTRS (Kevin Byrne, M.S.) , the Tissue Services Facility, and the Animal facility of the JHU-SKCCC for their support in this project. The publication costs of this article were defrayed in part by the payment of publication fees. Therefore, and solely to indicate this fact, this article is hereby marked ""advertisement"" in accordance with 18 USC section 1734."