Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

Cui, Fangbo; Liu, Qin; Li, Rutian; Shen, Jie; Wu, Puyuan; Yu, Lan; Hu, Weixin; Wu, Fenglei; Jiang, Chunping; Yue, Guofeng; Qian, Xiaoping; Jiang, Xiqun; Liu, Baorui

doi:10.2147/ijn.s60874

Cited by 15 publications

(5 citation statements)

References 36 publications

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“…Cui et al[158] synthesized a gelatinase-sensitive polymer nanocarrier that was loaded with miR-200c and acted on gastric cancer cells, and their results indicated that gastric cancer cells were significantly sensitized to radiotherapy. In addition, the expression of CD44 was down-regulated, the number of BGC823 cells (CD44 + ) was decreased, the cell invasion, metastasis, and anti-apoptosis ability were weakened, and the resistance characteristics of CSCs were decreased[158]. Moreover, other NDDSs have been used for targeted therapy of CSCs, such as nano-loaded genes, nano-loaded siRNA[159], and nano-compound both drugs[160].…”

Section: Other Methods For the Treatment Of Cscsmentioning

confidence: 99%

Targeting cancer stem cells in drug discovery: Current state and future perspectives

Zhou

Sun

et al. 2019

WJSC

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In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways ( e.g ., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication, survival, and differentiation. Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape. Therefore, multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs. Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials, and some inhibitors, such as vismodegib, sonidegib, and glasdegib, have been approved. Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein. The signal transducers and activators of transcription 3 (STAT3) inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers. Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development, which is another strategy for CSC therapy. In addition to the potential pharmacological inhibitors targeting CSC-related signaling pathways, other methods of targeting CSCs are available, such as nano-drug delivery systems, mitochondrion targeting, autophagy, hyperthermia, immunotherapy, and CSC microenvironment targeting. In addition, we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.

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Section: Other Methods For the Treatment Of Cscsmentioning

confidence: 99%

Targeting cancer stem cells in drug discovery: Current state and future perspectives

Zhou

Sun

et al. 2019

WJSC

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“…The 3D cultured model mimics in vivo microenvironment and has numerous different characteristics compared with 2D culture, which is a convenient method to induce CSC-like properties ( Chen et al, 2012 ; Xue et al, 2015b ; Usui et al, 2016 ). The combinatorial effects of epigenetic regulation and ionizing radiation contribute to eliminating CSCs have been reported ( Cui et al, 2014 ; Peitzsch et al, 2016 ; Kwon et al, 2017 ). MiRNAs showed differential expression profiles between 2D and 3D cells, and miR-29b-3p had the most dramatic negative change in cells of 3D compared with 2D cultures.…”

Section: Discussionmentioning

confidence: 99%

miR-29b-3p Increases Radiosensitivity in Stemness Cancer Cells via Modulating Oncogenes Axis

Pan

et al. 2021

Front. Cell Dev. Biol.

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Radioresistance conferred by cancer stem cells (CSCs) is the principal cause of the failure of cancer radiotherapy. Eradication of CSCs is a prime therapeutic target and a requirement for effective radiotherapy. Three dimensional (3D) cell-cultured model could mimic the morphology of cells in vivo and induce CSC properties. Emerging evidence suggests that microRNAs (miRNAs) play crucial roles in the regulation of radiosensitivity in cancers. In this study, we aim to investigate the effects of miRNAs on the radiosensitivity of 3D cultured stem-like cells. Using miRNA microarray analysis in 2D and 3D cell culture models, we found that the expression of miR-29b-3p was downregulated in 3D cultured A549 and MCF7 cells compared with monolayer (2D) cells. Clinic data analysis from The Cancer Genome Atlas database exhibited that miR-29b-3p high expression showed significant advantages in lung adenocarcinoma and breast invasive carcinoma patients’ prognosis. The subsequent experiments proved that miR-29b-3p overexpression decreased the radioresistance of cells in 3D culture and tumors in vivo through interfering kinetics process of DNA damage repair and inhibiting oncogenes RBL1, PIK3R1, AKT2, and Bcl-2. In addition, miR-29b-3p knockdown enhanced cancer cells invasion and migration capability. MiR-29b-3p overexpression decreased the stemness of 3D cultured cells. In conclusion, our results demonstrate that miR-29b-3p could be a sensitizer of radiation killing in CSC-like cells via inhibiting oncogenes expression. MiR-29b-3p could be a novel therapeutic candidate target for radiotherapy.

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“…Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis detection kit (Sigma) via flow cytometry. MKN-45 and AGS cells (2x10 5 ) were seeded into 6-well plates, treated with radiation of 6 Gy21 and cultured for 48 hrs. Each group was prepared in triplicate.…”

Section: Methodsmentioning

confidence: 99%

<p>MiR-203 acts as a radiosensitizer of gastric cancer cells by directly targeting ZEB1</p>

Jiang¹,

Jin²,

Tan³

et al. 2019

OTT

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Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Radiotherapy is one of the main strategies for GC treatment, while development of radioresistance limits the effectiveness. microRNA-203 (miR-203) has been reported to participate in progression of GC, whereas its interaction with radiosensitivity of GC and the related mechanism remain largely unclear. Methods: The expressions of miR-203 and zinc finger E-box binding homeobox 1 (ZEB1) were measured in GC tissues and cells by quantitative real-time polymerase chain reaction or western blot. Survival fraction, cell viability and apoptosis were measured in GC cells after treatment of radiation by colony formation, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT) assay or flow cytometry, respectively. Tumor volume and weight were detected in murine xenograft model after radiation treatment. The interaction between miR-203 and ZEB1 was explored by bioinformatics analysis and luciferase activity assay. Results: miR-203 expression was down-regulated and ZEB1 mRNA level was up-regulated in GC. The expression of miR-203 was associated with radiosensitivity of GC cells. Moreover, overexpression of miR-203 decreased survival fraction, cell viability and tumor growth but promoted cell apoptosis in radiation-treated GC cells. However, knockdown of miR-203 played an opposite effect. ZEB1 was validated as a target of miR-203, and it was involved in miR-203-mediated radiosensitivity of GC cells in vitro and in vivo. Conclusion: miR-203 promoted radiosensitivity of GC cells by targeting ZEB1, indicating miR-203 as a promising radiosensitizer for GC treatment.

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Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

Cited by 15 publications

References 36 publications

Targeting cancer stem cells in drug discovery: Current state and future perspectives

Targeting cancer stem cells in drug discovery: Current state and future perspectives

miR-29b-3p Increases Radiosensitivity in Stemness Cancer Cells via Modulating Oncogenes Axis

<p>MiR-203 acts as a radiosensitizer of gastric cancer cells by directly targeting ZEB1</p>

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