Cancer Research and Treatment

Original Articles

Tumor Growth Suppression and Enhanced Radioresponse by an Exogenous Epidermal Growth Factor in Mouse Xenograft Models with A431 Cells: Yu Jin Lim, Sang-Rok Jeon, Jae Moon Koh, Hong-Gyun Wu; Cancer Res Treat. 2015;47(4):921-930. Published online January 7, 2015; DOI: https://doi.org/10.4143/crt.2014.153

Purpose
The purpose of this study was to evaluate whether an exogenous epidermal growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo.
Materials and Methods
BALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cells in the right hind legs were divided into five groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung, and kidney tissues were investigated. Additionally, tumors were subjected to immunohistochemistry staining with caspase-3.
Results
EGF for 6 days decreased tumor volume, but it approached the level of the control group at the end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20 days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistry revealed that mice in group V showed stronger intensity than those in group IV. There were no abnormal histological findings upon H&E staining of the normal organs.
Conclusion
EGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431 cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design of fractionated irradiation.

Citations

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Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR): A Targeted Protein Degradation Toolbox
Dirk H. Siepe, Lora K. Picton, K. Christopher Garcia
ACS Synthetic Biology.2023; 12(4): 1081. CrossRef
Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers
Jae Sik Kim, Joo Ho Lee, Sang-Rok Jeon, Yongsub Kim, Seung Hyuck Jeon, Hong-Gyun Wu
Cancer Research and Treatment.2023; 55(3): 737. CrossRef
DNA damage alters EGFR signaling and reprograms cellular response via Mre-11
Yael Volman, Ruth Hefetz, Eithan Galun, Jacob Rachmilewitz
Scientific Reports.2022;[Epub] CrossRef
Efficacy of combined icotinib and pemetrexed in EGFR mutant lung adenocarcinoma cell line xenografts
Jiadong Cui, Yan Zhang, Di Su, Tao Li, Yu Li
Thoracic Cancer.2018; 9(9): 1156. CrossRef
Biased signaling downstream of epidermal growth factor receptor regulates proliferative versus apoptotic response to ligand
Remah Ali, Wells Brown, Stephen Connor Purdy, V. Jo Davisson, Michael K. Wendt
Cell Death & Disease.2018;[Epub] CrossRef
The paradoxical functions of EGFR during breast cancer progression
Remah Ali, Michael K Wendt
Signal Transduction and Targeted Therapy.2017;[Epub] CrossRef
Efficacy of radiotherapy for the treatment of cystic echinococcosis in naturally infected sheep
Rui Mao, Wen-Bao Zhang, Hong-Zhi Qi, Tao Jiang, Ge Wu, Peng-Fei Lu, Abudula Ainiwaer, Ge Shang, Lin Xu, Jie Hao, Xi Shou, Hai-Tao Li, Jun Li, Song-An Zhang, Yong-Xing Bao, Hao Wen
Infectious Diseases of Poverty.2017;[Epub] CrossRef
Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis
Le Phuc, Akiyoshi Taniguchi
International Journal of Molecular Sciences.2017; 18(6): 1301. CrossRef

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Sequence-Dependent Radiosensitization of Histone Deacetylase Inhibitors Trichostatin A and SK-7041: Jin Ho Kim, Il Han Kim, Jin Hee Shin, Hak Jae Kim, In Ah Kim; Cancer Res Treat. 2013;45(4):334-342. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.334

Abstract PDF PubReader ePub

PURPOSE
This preclinical study is to determine whether the capacity of histone deacetylase (HDAC) inhibitors to enhance radiation response depends on temporal sequences of HDAC inhibition and irradiation.
MATERIALS AND METHODS
The effects of HDAC inhibitors trichostatin A (TSA) and SK-7041 on radiosensitivity in human lung cancer cells were examined using a clonogenic assay, exposing cells to HDAC inhibitors in various sequences of HDAC inhibition and radiation. We performed Western blot of acetylated histone H3 and flow cytometry to analyze cell cycle phase distribution.
RESULTS
TSA and SK-7041 augmented radiation cell lethality in an exposure time-dependent manner when delivered before irradiation. The impact of TSA and SK-7041 on radiosensitivity rapidly diminished when HDAC inhibition was delayed after irradiation. Radiation induced the acetylation of histone H3 in cells exposed to TSA, while irradiation alone had no effect on the expression of acetylated histone H3 in TSA-naive cells. Preirradiation exposure to TSA abrogated radiation-induced G2/M-phase arrest. When delivered after irradiation, TSA had no effect on the peak of radiation-induced G2/M-phase arrest.
CONCLUSION
TSA and SK-7041 enhances radiosensitivity only when delivered before irradiation. Unless proven otherwise, it seems prudent to apply scheduling including preirradiation HDAC inhibition so that maximal radiosensitization is obtained.

Citations

Citations to this article as recorded by

Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview
Elsie Neo Seane, Shankari Nair, Charlot Vandevoorde, Anna Joubert
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Investigation of geroprotective and radioprotective effects of berberine and trichostatin A on the model of Drosophila melanogaster
N. Ulyasheva, E. Proshkina, M. Shaposhnikov, A. Moskalev
Proceedings of the Komi Science Centre of the Ural Division of the Russian Academy of Sciences.2023; 0(6): 93. CrossRef
Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells
Fengqiu Zhang, Changsheng Shao, Zhu Chen, Yalin Li, Xumiao Jing, Qing Huang
Radiation Research.2021;[Epub] CrossRef
Time-sequential change in immune-related gene expression after irradiation in glioblastoma: next-generation sequencing analysis
Yi-Jun Kim, Kwangsoo Kim, Soo Yeon Seo, Juyeon Yu, Il Han Kim, Hak Jae Kim, Chul-Kee Park, Kye Hwa Lee, Junjeong Choi, Myung Seon Song, Jin Ho Kim
Animal Cells and Systems.2021; 25(4): 245. CrossRef
Is level of acetylation directly correlated to radiation sensitivity of cancer cell?
Fengqiu Zhang, Zhu Chen, Changsheng Shao, Qing Huang
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.2019; 813: 13. CrossRef
Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro
Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Cancer Research and Treatment.2019; 51(2): 696. CrossRef
Psammaplin A-Modified Novel Radiosensitizers for Human Lung Cancer and Glioblastoma Cells
Chan Woo Wee, Jin Ho Kim, Hak Jae Kim, Hyun-Cheol Kang, Soo Youn Suh, Beom Soo Shin, Eunsook Ma, Il Han Kim
Journal of Radiation Protection and Research.2019; 44(1): 15. CrossRef
Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization
Jin Ho Kim, Sung Ho Moon, Mina No, Jae Jin Kim, Eun Jung Choi, Bong Jun Cho, Jae Sung Kim, Il Han Kim, In Ah Kim
Cancer Research and Treatment.2016; 48(3): 1130. CrossRef

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