ABSTRACT BACKGROUND Fibroblast growth factor receptor (FGFR) signaling influenced tumour occurrence and development. Overexpression of FGFR had been observed in many types of cancers,

including colon cancer. FGFR inhibitor is considered to be effective in treating colon cancer patients. METHODS First, the kinase inhibition rate was determined. MTT, western blotting,

colony formation, EdU and comet assays were performed to evaluate the anti-tumour effects of F1-7 in vitro. RNA-seq and bioinformatics analysis were used for further verification.

Additionally, a xenograft model was generated to investigate the anti-tumour effect of F1-7. RESULTS F1-7 can inhibit the proliferation of colon cancer cells in vitro. It could significantly

cell cycle arrest and inhibition of cell metastasis and cell apoptosis. Mouse model experiments also confirmed that F1-7 could inhibit tumour growth by inhibiting the FGFR pathway.

CONCLUSIONS F1-7 exhibits anti-tumour activity by inhibiting the FGFR pathway. It could be a novel therapeutic agent for targeting colon cancer cells. Access through your institution Buy or

subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 24 print issues and online

access $259.00 per year only $10.79 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which

are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS

DISRUPTION OF THE Β-CATENIN DESTRUCTION COMPLEX VIA EPHEXIN1-AXIN1 INTERACTION PROMOTES COLORECTAL CANCER PROLIFERATION Article Open access 01 January 2025 UBXN2A SUPPRESSES THE

RICTOR-MTORC2 SIGNALING PATHWAY, AN ESTABLISHED TUMORIGENIC PATHWAY IN HUMAN COLORECTAL CANCER Article 10 April 2023 FMR1 PROMOTES THE PROGRESSION OF COLORECTAL CANCER CELL BY STABILIZING

EGFR MRNA IN AN M6A-DEPENDENT MANNER Article Open access 08 November 2022 DATA AVAILABILITY The data used to support the findings of this study are available from the corresponding author

upon request. REFERENCES * Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–91.

Article  PubMed  Google Scholar  * Murakawa T. Past, present, and future perspectives of pulmonary metastasectomy for patients with advanced colorectal cancer. Surg Today. 2021;51:204–11.

Article  PubMed  Google Scholar  * Cheng YD, Yang H, Chen GQ, Zhang ZC. Molecularly targeted drugs for metastatic colorectal cancer. Drug Des Devel Ther. 2013;7:1315–22. PubMed Central 

PubMed  Google Scholar  * Touat M, Ileana E, Postel-Vinay S, Andre F, Soria JC. Targeting FGFR signaling in cancer. Clin Cancer Res. 2015;21:2684–94. Article  CAS  PubMed  Google Scholar  *

Formisano L, Lu Y, Servetto A, Hanker AB, Jansen VM, Bauer JA, et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun. 2019;10:1373. Article

  PubMed  Google Scholar  * Porta R, Borea R, Coelho A, Khan S, Araujo A, Reclusa P, et al. FGFR a promising druggable target in cancer: Molecular biology and new drugs. Crit Rev Oncol

Hematol. 2017;113:256–67. Article  PubMed  Google Scholar  * Gozgit JM, Wong MJ, Moran L, Wardwell S, Mohemmad QK, Narasimhan NI, et al. Ponatinib (AP24534), a multitargeted pan-FGFR

inhibitor with activity in multiple FGFR-amplified or mutated cancer models. Mol Cancer Ther. 2012;11:690–9. Article  CAS  PubMed  Google Scholar  * Ma WW, Xie H, Fetterly G, Pitzonka L,

Whitworth A, LeVea C, et al. A phase Ib study of the FGFR/VEGFR inhibitor dovitinib with gemcitabine and capecitabine in advanced solid tumor and pancreatic cancer patients. Am J Clin Oncol.

2019;42:184–9. Article  CAS  PubMed  Google Scholar  * Guffanti F, Chila R, Bello E, Zucchetti M, Zangarini M, Ceriani L, et al. In vitro and in vivo activity of lucitanib in FGFR1/2

amplified or mutated cancer models. Neoplasia. 2017;19:35–42. Article  CAS  PubMed  Google Scholar  * Steegmann JL, Baccarani M, Breccia M, Casado LF, Garcia-Gutierrez V, Hochhaus A, et al.

European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30:1648–71. Article  CAS  PubMed  Google

Scholar  * Gavine PR, Mooney L, Kilgour E, Thomas AP, Al-Kadhimi K, Beck S, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor

tyrosine kinase family. Cancer Res. 2012;72:2045–56. Article  CAS  PubMed  Google Scholar  * Komla-Ebri D, Dambroise E, Kramer I, Benoist-Lasselin C, Kaci N, Le Gall C, et al. Tyrosine

kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. J Clin Invest. 2016;126:1871–84. Article  PubMed  Google Scholar  * Wu D, Guo M, Min X, Dai S, Li M,

Tan S, et al. LY2874455 potently inhibits FGFR gatekeeper mutants and overcomes mutation-based resistance. Chem Commun (Camb). 2018;54:12089–92. Article  CAS  Google Scholar  * Liu Q, Yu S,

Zhao W, Qin S, Chu Q, Wu K. EGFR-TKIs resistance via EGFR-independent signaling pathways. Mol Cancer. 2018;17:53. Article  PubMed  Google Scholar  * Lin S, Yang L, Yao Y, Xu L, Xiang Y, Zhao

H, et al. Flubendazole demonstrates valid antitumor effects by inhibiting STAT3 and activating autophagy. J Exp Clin Cancer Res. 2019;38:293. Article  PubMed  Google Scholar  * Qiu Y, Xiao

Z, Wang Y, Zhang D, Zhang W, Wang G, et al. Optimization and anti-inflammatory evaluation of methyl gallate derivatives as a myeloid differentiation protein 2 inhibitor. Bioorg Med Chem.

2019;27:115049. Article  CAS  PubMed  Google Scholar  * Lu HR, Meng LH, Huang M, Zhu H, Miao ZH, Ding J. DNA damage, c-myc suppression and apoptosis induced by the novel topoisomerase II

inhibitor, salvicine, in human breast cancer MCF-7 cells. Cancer Chemother Pharmacol. 2005;55:286–94. Article  CAS  PubMed  Google Scholar  * Yu G, Wang LG, Han Y, He QY. clusterProfiler: an

R package for comparing biological themes among gene clusters. OMICS. 2012;16:284–7. Article  CAS  PubMed  Google Scholar  * Wenger T, Miller D, Evans K. FGFR Craniosynostosis Syndromes

Overview. In: MP Adam et al. (eds). GeneReviews®. October 20, 1998. * Liu Y, Cao M, Cai Y, Li X, Zhao C, Cui R. Dissecting the role of the FGF19-FGFR4 signaling pathway in cancer development

and progression. Front Cell Dev Biol. 2020;8:95. Article  PubMed  Google Scholar  * von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional

associations between proteins. Nucleic Acids Res. 2003;31:258–61. Article  Google Scholar  * Zhou L, Wang S, Cao L, Ren X, Li Y, Shao J, et al. Lead acetate induces apoptosis in Leydig cells

by activating PPARgamma/caspase-3/PARP pathway. Int J Environ Health Res. 2021;31:34–44. Article  CAS  PubMed  Google Scholar  * Maes ME, Grosser JA, Fehrman RL, Schlamp CL, Nickells RW.

Completion of BAX recruitment correlates with mitochondrial fission during apoptosis. Sci Rep. 2019;9:16565. Article  CAS  PubMed  Google Scholar  * Willis S, Day CL, Hinds MG, Huang DC. The

Bcl-2-regulated apoptotic pathway. J Cell Sci. 2003;116:4053–6. Article  CAS  PubMed  Google Scholar  * Kuo LJ, Yang LX. Gamma-H2AX—a novel biomarker for DNA double-strand breaks. Vivo.

2008;22:305–9. CAS  Google Scholar  * Yang Y, Xue K, Li Z, Zheng W, Dong W, Song J, et al. [Corrigendum] cMyc regulates the CDK1/cyclin B1 dependentG2/M cell cycle progression by histone H4

acetylation in Raji cells. Int J Mol Med. 2019;44:1988. PubMed Central  PubMed  Google Scholar  * Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev.

2014;34:280–300. Article  CAS  PubMed  Google Scholar  * Hall A. The cytoskeleton and cancer. Cancer Metastasis Rev. 2009;28:5–14. Article  PubMed  Google Scholar  * Fuhrmann A, Banisadr A,

Beri P, Tlsty TD, Engler AJ. Metastatic state of cancer cells may be indicated by adhesion strength. Biophys J. 2017;112:736–45. Article  CAS  PubMed  Google Scholar  * Venetsanakos E,

Brameld KA, Phan VT, Verner E, Owens TD, Xing Y, et al. The irreversible covalent fibroblast growth factor receptor inhibitor PRN1371 exhibits sustained inhibition of FGFR after drug

clearance. Mol Cancer Ther. 2017;16:2668–76. Article  CAS  PubMed  Google Scholar  * Tan L, Wang J, Tanizaki J, Huang Z, Aref AR, Rusan M, et al. Development of covalent inhibitors that can

overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci USA. 2014;111:E4869–4877. CAS  PubMed Central  PubMed  Google Scholar  * Lu X, Chen H, Patterson AV, Smaill

JB, Ding K. Fibroblast growth factor receptor 4 (FGFR4) selective inhibitors as hepatocellular carcinoma therapy: advances and prospects. J Med Chem. 2019;62:2905–15. Article  CAS  PubMed 

Google Scholar  * Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, et al. Futibatinib is a novel irreversible FGFR 1-4 inhibitor that shows selective antitumor activity against

FGFR-deregulated tumors. Cancer Res. 2020;80:4986–97. Article  CAS  PubMed  Google Scholar  * Kang X, Lin Z, Xu M, Pan J, Wang ZW. Deciphering role of FGFR signalling pathway in pancreatic

cancer. Cell Prolif. 2019;52:e12605. Article  PubMed  Google Scholar  Download references FUNDING This study was supported by the National Natural Science Funding of China (81473242,

21877085 and 21602159). AUTHOR INFORMATION Author notes * These authors contributed equally: Yanan Liu, Liting Zhang. AUTHORS AND AFFILIATIONS * School of Pharmaceutical Sciences, Wenzhou

Medical University, 325035, Wenzhou, Zhejiang, China Yanan Liu, Liting Zhang, Xiaolu Chen, Daoxing Chen, Xueqin Shi, Jiali Song, Jianzhang Wu, Fengyu Huang, Qinqin Xia, Xiaohui Zheng & 

Yuepiao Cai * Department of Colon and Rectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Youqun Xiang Authors * Yanan Liu View author

publications You can also search for this author inPubMed Google Scholar * Liting Zhang View author publications You can also search for this author inPubMed Google Scholar * Xiaolu Chen

View author publications You can also search for this author inPubMed Google Scholar * Daoxing Chen View author publications You can also search for this author inPubMed Google Scholar *

Xueqin Shi View author publications You can also search for this author inPubMed Google Scholar * Jiali Song View author publications You can also search for this author inPubMed Google

Scholar * Jianzhang Wu View author publications You can also search for this author inPubMed Google Scholar * Fengyu Huang View author publications You can also search for this author

inPubMed Google Scholar * Qinqin Xia View author publications You can also search for this author inPubMed Google Scholar * Youqun Xiang View author publications You can also search for this

author inPubMed Google Scholar * Xiaohui Zheng View author publications You can also search for this author inPubMed Google Scholar * Yuepiao Cai View author publications You can also

search for this author inPubMed Google Scholar CONTRIBUTIONS YC and XZ contributed to the conception of the study; YL, LZ and XC performed the experiment; FH and XS revised and complemented

the figure; DC and JS contributed significantly to analysis and manuscript preparation; YL performed the data analyses and wrote the manuscript; JW, QX and YX helped perform the analysis

with constructive discussions. CORRESPONDING AUTHORS Correspondence to Youqun Xiang, Xiaohui Zheng or Yuepiao Cai. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing

interests. ETHICS APPROVAL AND CONSENT TO PARTICIPATE Our study was approved by ‘the Laboratory Animal Centre, Wenzhou Medical University’ (wydw2020-0886). CONSENT FOR PUBLICATION No

personal data or identifying information are being submitted. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps

and institutional affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Liu, Y., Zhang, L.,

Chen, X. _et al._ The novel FGFR inhibitor F1-7 induces DNA damage and cell death in colon cells. _Br J Cancer_ 127, 1014–1025 (2022). https://doi.org/10.1038/s41416-022-01878-4 Download

citation * Received: 28 June 2021 * Revised: 19 May 2022 * Accepted: 31 May 2022 * Published: 17 June 2022 * Issue Date: 05 October 2022 * DOI: https://doi.org/10.1038/s41416-022-01878-4

SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to

clipboard Provided by the Springer Nature SharedIt content-sharing initiative