Feng-Liao-Chang-Wei-Kang Combined with 5-Fluorouracil Synergistically Suppresses Colitis-Associated Colorectal Cancer via the IL-6/STAT3 Signalling Pathway

Background. Colitis-associated colorectal cancer (CAC) develops from active colonic inflammation, which is characterized by the production of proinflammatory cytokines that can induce mutations. IL-6 is produced by multiple cell types located within the tumor microenvironment including tumor-infiltrating immune cells, stromal cells, and the tumor cells themselves. The aim of our study was to explore the mechanism of Feng-Liao-Chang-Wei-Kang (FLCWK) and 5-fluorouracil (5-FU) in treating CAC. Method. HCT116 cells were treated with 5-FU in the absence or presence of FLCWK. Cell proliferation was assayed by MTT assays. Apoptosis and the cell cycle phases were detected by flow cytometry. Western blotting and Q-PCR assays were used to detect the expression levels of proteins and genes related to the IL-6/STAT3 signalling pathway. A mouse model for CAC was established by treating animals with 12.5 mg/kg azoxymethane (AOM) followed by 3 cycles of 2.5% dextran sodium sulphate (DSS). The associated pathological changes were determined after haematoxylin and eosin (H&E) staining. The expression of related proteins and genes in various tissues was examined using immunofluorescence techniques. Results. FLCWK enhanced the ability of 5-FU to promote apoptosis by inhibiting the proliferation of HCT116 cells and blocking the IL-6/STAT3 pathway. FLCWK combined with 5-FU reduced the number and size of colon tumors in mice with CAC and significantly increased their survival rate. In the CAC model, FLCWK synergized with 5-FU to inhibit the phosphorylation of STAT3, preventing IL-6/STAT3 signal transduction and thus further inducing apoptosis and inhibition of colon cancer cell proliferation. Conclusion. FLCWK can inhibit the activation of STAT3 by reducing the production of IL-6, thereby increasing the occurrence of colitis-related colorectal cancer with 5-FU.

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Suppression of LINC00460 mediated the sensitization of HCT116 cells to ionizing radiation by inhibiting epithelial–mesenchymal transition

Toxicology Research ◽

10.1093/toxres/tfaa010 ◽

2020 ◽

Vol 9 (2) ◽

pp. 107-116

Author(s):

Jiani Zhang ◽

Lixin Ding ◽

Gaofeng Sun ◽

Huacheng Ning ◽

Ruixue Huang

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Ionizing Radiation ◽

Epithelial Mesenchymal Transition ◽

Hct116 Cell ◽

Cell Types ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Mesenchymal Transition ◽

Hct116 Cells

Abstract Radiation resistance is the most common challenge for improving radiotherapy. The mechanisms underlying the development of radioresistance remain poorly understood. This study aims to explore the role of LINC00460 in ionizing radiation-induced radioresistance as well as the mechanisms by which LINC00460 is regulated by radiation exposure. The expression of LINC00460 was measured. Cell proliferation and colony formation were measured in HCT116 cells after treatment by radiation. The development of epithelial–mesenchymal transition (EMT) was determined with or without knockdown LINC00460 expression using western blot analysis. Transcription activity was determined using a series of LINC00460-promoter luciferase reporter gene vectors. LINC00460 expression was significantly higher in HCT116 cells, relative to other cell types, with LINC00460 expression significantly affecting HCT116 cell proliferation. Suppression of LINC00460 inhibits EMT development in HCT116 cells via regulation of ZEB1 expression. Furthermore, LINC00460 expression was induced by irradiation via the activation of c-jun transcription factor-binding element located on the LINC00460 promoter. LINC00460 was shown to play a crucial role in EMT-associated progression of colorectal cancer, indicating that LINC00460 may be an indicator or new potential therapeutic target for colorectal cancer radiosensitization.

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A438079 affects colorectal cancer cell proliferation, migration, apoptosis, and pyroptosis by inhibiting the P2X7 receptor

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.04.076 ◽

2021 ◽

Vol 558 ◽

pp. 147-153

Author(s):

Ying Zhang ◽

Fang Li ◽

Lili Wang ◽

Yi Lou

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

P2x7 Receptor ◽

Colorectal Cancer Cell ◽

Cancer Cell Proliferation

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Regulation of UHRF 1 by micro RNA ‐9 modulates colorectal cancer cell proliferation and apoptosis

Cancer Science ◽

10.1111/cas.12689 ◽

2015 ◽

Vol 106 (7) ◽

pp. 833-839 ◽

Cited By ~ 35

Author(s):

Mingchen Zhu ◽

Yijun Xu ◽

Mengyuan Ge ◽

Zhen Gui ◽

Feng Yan

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Micro Rna ◽

Colorectal Cancer Cell ◽

Cancer Cell Proliferation ◽

Proliferation And Apoptosis

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Polyamide Amine Dendrimer Nanoparticles Conjugated with Cis-Diamminedichloroplatinum (CDDP) and miRNA-200c Inhibitor Suppresses Lung Cancer Cell Proliferation

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2822 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1760-1768

Author(s):

Fang Zhang ◽

Jili Zou ◽

Dandan Huang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Cell Proliferation ◽

Lung Cancer Cell ◽

Targeting Delivery ◽

Apoptosis Related Protein ◽

Related Proteins ◽

Exclusion Method ◽

Inhibit Cell Proliferation ◽

Excellent Stability

Our study elucidates the effect of folate polyamide amine dendrimer nanoparticles targeting delivery of miRNA-200c inhibitor and CDDP on lung cancer cells proliferation. We established polyamide amine dendrimer nanoparticles binding with CDDP and miRNA-200c inhibitor (Den-PEI-CDDP-siRNA-FA), TEM was employed to detect the morphology of nanoparticles. Agarose gel assay was selected for stabilization test. Cell proliferation were detected by trypanosoma blue exclusion method. The expression of miRNA-200c targeted APKPA12 and apoptosis-related proteins were detected by Western blot and PCR. Finally, apoptosis was analyzed by flow cytometry. Den-PEI-CDDP-siRNA-FA nanoparticles showed excellent stability and drug encapsulation ability. Nanoparticles targeting for FRA to co-deliver siRNA and CDDP could significantly promote cell apoptosis, increase apoptosis-related protein expression, and inhibit cell proliferation. Besides, nanoparticles exerted less venomous effect than untargeted nanoparticles in MRC9 lung fibroblast. Den nanoparticle targeting FRA might be used as the carrier for joint applications with siRNA and CDDP for treating lung cancer.

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si-SNHG5-FOXF2 inhibits TGF-β1-induced fibrosis in human primary endometrial stromal cells by the Wnt/β-catenin signalling pathway

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01990-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Limin Liu ◽

Guobin Chen ◽

Taoliang Chen ◽

Wenjuan Shi ◽

Haiyan Hu ◽

...

Keyword(s):

Cell Proliferation ◽

Stromal Cells ◽

Target Genes ◽

Cell Model ◽

Ex Vivo ◽

Signalling Pathway ◽

Endometrial Stromal Cells ◽

Downstream Target ◽

Related Proteins ◽

Tgf Β1

Abstract Background Intrauterine adhesions (IUAs) are manifestations of endometrial fibrosis characterized by inflammation and fibrinogen aggregation in the extracellular matrix (ECM). The available therapeutic interventions for IUA are insufficiently effective in the clinical setting for postoperative adhesion recurrence and infertility problems. In this study, we investigated whether si-SNHG5-FOXF2 can serve as a molecular mechanism for the inhibition of IUA fibrosis ex vivo. Methods FOXF2, TGF-β1 and collagen expression levels were measured by microarray sequencing analysis in three normal endometrium groups and six IUA patients. We induced primary human endometrial stromal cells (HESCs) into myofibroblasts (MFs) to develop an IUA cell model with various concentrations of TGF-β1 at various times. Downstream target genes of FOXF2 were screened by chromatin immunoprecipitation combined with whole-genome high-throughput sequencing (ChIP-seq). We investigated ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs with FOXF2 downregulation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB), immunohistochemistry (IHC), flow cytometry, ethylenediurea (EdU) and CCK8 assays. We identified long noncoding RNAs (lncRNA) SNHG5 as the upstream regulatory gene of FOXF2 through RNA immunoprecipitation (RIP), RNA pulldown and fluorescence in situ hybridization (FISH). Finally, we examined FOXF2 expression, ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs upon FOXF2 downregulation. Results FOXF2 was highly expressed in the endometrium of patients with IUA. Treatment of primary HESCs with 10 ng/ml TGF-β1 for 72 h was found to be most effective for developing an IUA cell model. FOXF2 regulated multiple downstream target genes, including collagen, vimentin (VIM) and cyclin D2/DK4, by ChIP-seq and ChIP-PCR. FOXF2 downregulation inhibited TGF-β1-mediated primary HESC fibrosis, including ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related protein expression. We identified lncRNA SNHG5 as an upstream gene that directly regulates FOXF2 by RIP-seq, qRT-PCR, WB and FISH. SNHG5 downregulation suppressed FOXF2 expression in the IUA cell model, resulting in synergistic repression of the Wnt/β-catenin pathway, thereby altering TGF-β1-mediated ECM aggregation in endometrial stromal cells ex vivo. Conclusions Regulation of the Wnt/β-catenin signalling pathway and ECM formation by si-SNHG5-FOXF2 effectively inhibited the profibrotic effect of TGF-β1 on primary HESCs. This finding can provide a molecular basis for antagonizing TGF-β1-mediated fibrosis in primary HESCs.

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