Long term exposure to γ‑rays induces radioresistance and enhances the migration ability of bladder cancer cells

Mao, Guangmin; Yao, Ye; Kong, Zhaolu

doi:10.3892/mmr.2018.9605

Cited by 3 publications

(5 citation statements)

References 25 publications

(25 reference statements)

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“…Moreover, our results are also consistent with the reported accelerated repopulation after clinical radiotherapy (49). In our study, radioresistant cells also exhibited increased migration and anti-apoptotic ability, consistent with previous reports (50). Interestingly, the morphology changes observed in NF639R cells, including reduction and elongation of cell bodies, are similar to the cells undergoing epithelial-mesenchymal transition (EMT).…”

Section: Discussionsupporting

confidence: 93%

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells

Feng¹,

Fan²,

Yu³

et al. 2021

Ann Transl Med

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Background: Acquired radioresistant cells exhibit many characteristic changes which may influence cancer progression and further treatment options. The purpose of this study is to investigate the changes of radioresistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells on both phenotypic and molecular levels. Methods:We established an acquired radioresistant cell line from its parental NF639 cell line (HER2positive) by fractionated radiation and assessed changes in cellular morphology, proliferation, migration, anti-apoptosis activity, basal reactive oxygen species (ROS) level and energy metabolism. RNA-sequencing (RNA-seq) was also used to reveal the potential regulating genes and molecular mechanisms associated with the acquired changed phenotypes. Real-time PCR was used to validate the results of RNA-seq.Results: The NF639R cells exhibited increased radioresistance and enhanced activity of proliferation, migration and anti-apoptosis, but decreased basal ROS. Two main energy metabolism pathways, mitochondrial respiration and glycolytic, were also upregulated. Furthermore, 490 differentially expressed genes were identified by RNA-seq. Enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed many differently expressed genes were significantly enriched in cell morphology, proliferation, migration, anti-apoptosis, antioxidation, tumor stem cells and energy metabolism and the signaling cascades such as the transforming growth factor-β, Wnt, Hedgehog, vascular endothelial growth factor, retinoic acid-inducible gene I (RIG-I)-like receptor, Toll-like receptor and nucleotide oligomerization domain (NOD)-like receptor were significantly altered in NF639R cells. Conclusions:In clinical radiotherapy, repeat radiotherapy for short-term recurrence of breast cancer may result in enhanced radioresistance and promote malignant progression. Our research provided hints to understand the tumor resistance to radiotherapy de novo and recurrence with a worse prognosis following radiotherapy.

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Section: Discussionsupporting

confidence: 93%

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells

Feng¹,

Fan²,

Yu³

et al. 2021

Ann Transl Med

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“…3A). Consistent with previous reports (18,19), increased levels of pSTAT3 and MMP-2/9 were detected in both RR cell types. Also, the differences in two STAT3-based CSC-related signaling pathways, [KMT1A/GATA3/STAT3 (21) and JAK/STAT3 (27)] were assessed between parental BCa cells and their RR counterparts.…”

Section: Elevated Stat3 Phosphorylation In Rr Bca Cells Is Associatedsupporting

confidence: 93%

“…Our previous study reported that FI increases STAT3 phosphorylation in BCa cells (18). STAT3 phosphorylation also suppressed the RR of glioblastoma stem cells, and was associated with improved patient prognosis (33).…”

Section: Discussionmentioning

confidence: 93%

“…It is involved in epithelial-to-mesenchymal transition (EMT)-associated pathways, which are hypothesized to be the primary mechanisms for CSC generation (16), and has the ability to promote cancer progression by regulating the activity of CSCs (17). Moreover, our previous studies revealed that high levels of STAT3 phosphorylation are closely associated with the acquired radiation resistance (ARR) of urinary system tumors (18,19). The present study aimed to elucidate the role of STAT3 in RR and its association with the CSC phenotype in BCa cells.…”

Section: Introductionmentioning

confidence: 99%

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STAT3 enhances radiation-induced tumor migration, invasion and stem-like properties of bladder cancer

Wang

Mao

et al. 2020

Mol Med Rep

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Bladder cancer (BCa) is the most common cancer of the human urinary system, and is associated with poor patient prognosis and a high recurrence rate. Cancer stem cells (CSCs) are the primary cause of tumor recurrence and metastasis, possessing self-renewal properties and resistance to radiation therapy. Our previous studies indicated that phosphorylated signal transduction and transcription activator 3 (STAT3) may be a potential biomarker to predict radiation tolerance and tumor recurrence in patients with BCa, following conventional radiotherapy. The aim of the present study was to investigate the underlying mechanism of STAT3 in the radio-resistance of BCa cells. It was found that fractionated irradiation promoted the activation of two STAT3-associated CSCs signaling pathways in BCa cells, namely suppressor of variegation 3-9 homolog 1/GATA binding protein 3/STAT3 and Janus kinase 2/STAT3. Surviving cells exhibited elevated migratory and invasive abilities, enhanced CSC-like characteristics and radio-resistance. Furthermore, knockdown of STAT3 expression or inhibition of STAT3 activation markedly decreased the self-renewal ability and tumorigenicity of radiation-resistant BCa cells. Kaplan-Meier analysis revealed that decreased STAT3 mRNA levels were associated with increased overall survival times in patients with BCa. Taken together, these data indicated that STAT3 may be an effective therapeutic target for inhibiting the progression, metastasis and recurrence of BCa in patients receiving radiotherapy.

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“…In order to explore the mechanism of BCa recurrence and treatment tolerance after clinical radiotherapy, we established ARR cell model 5637R and T24R ( Fig. 1 A) by subjected human BCa cell lines 5637 and T24 to long-term IR as described previously [11] . With tumor microsphere culture and soft agar colony anchoring assay, we noticed that ARR cells (5637R & T24R) exhibited enhanced CSC properties compared to the parental cells (5637 & T24), respectively.…”

Section: Resultsmentioning

confidence: 99%

EZH2 targeting to improve the sensitivity of acquired radio-resistance bladder cancer cells

Zhang¹,

Ma²,

Wang³

et al. 2022

Translational Oncology

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Highlights Fractionated irradiation enriched stem cell-like characteristics and increased EZH2 expression of BCa cells. Down-regulation of EZH2 reduced the radio-resistance phenotype and decreased the microsphere formation and DNA repair abilities of BCa cells. Down-regulation of EZH2 affected the autophagic-flux stability of BCa cells. Down-regulation of EZH2 inhibited ARR cells growth in vivo.

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Long term exposure to γ‑rays induces radioresistance and enhances the migration ability of bladder cancer cells

Cited by 3 publications

References 25 publications

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells

STAT3 enhances radiation-induced tumor migration, invasion and stem-like properties of bladder cancer

EZH2 targeting to improve the sensitivity of acquired radio-resistance bladder cancer cells

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