scholarly journals Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiawa Mao ◽  
Nanzhang ◽  
Jiaquao Xiao ◽  
Huifeng Wu ◽  
Kefeng Ding
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Cancer Cell Line ◽  
Hypoxic Condition ◽  
Underlying Mechanism ◽  
Bladder Cancer Cell Line ◽  
Hypoxic Conditions ◽  
Bladder Cancer Cells ◽  
Autophagy Pathway

Purpose. To investigate the effect of hypoxia on chemoresistance and the underlying mechanism in bladder cancer cells. Methods. BIU-87 bladder cancer cell line was treated with cisplatin under hypoxic and normoxic conditions and tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting. All the data were expressed as mean ± standard   error from three independent experiments and analyzed by multiple t -tests. Results. Apoptosis of bladder cancer cells caused by cisplatin was attenuated in hypoxic conditions. Hypoxia enhanced autophagy caused by cisplatin. The autophagy inhibitor and HIF-1α inhibitor can reverse the chemoresistance in hypoxic condition. Apoptosis and autophagy of bladder cancer cells were downregulated by HIF-1α inhibitor YC-1. Hypoxia-induced autophagy enhanced chemoresistance to cisplatin via the HIF-1 signaling pathway. Conclusion. Resistance to cisplatin in BIU-87 bladder cancer cells under hypoxic conditions can be explained by activation of autophagy, which is regulated by HIF-1α-associated signaling pathways. The hypoxia–autophagy pathway may be a target for improving the efficacy of cisplatin chemotherapy in bladder cancer.

Effect of defective ERCC2 on cisplatin and ionizing radiation (IR) sensitivity in bladder cancer cells.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 333-333
Author(s):  
Qiang Li ◽  
Andrew Bell ◽  
Emmet Jordan ◽  
Sizhi Paul Gao ◽  
Jennifer Ma ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Bladder Cancer Cells ◽  
Bladder Sparing ◽  
Mutant Cells

333 Background: Genetic alterations within ERCC2 correlate with extraordinary responses to neoadjuvant cisplatin-based chemotherapy and bladder-sparing ionizing radiation (IR) in muscle-invasive bladder cancer (MIBC). Two studies correlated ERCC2 mutations with pathologic response to chemotherapy and improved disease-free and bladder intact survival following trimodality therapy. We sought to characterize the biological significance of these mutations in bladder cancer cells using CRISPR/Cas9-mediated ablation of ERCC2 function. Methods: The ERCC2 T484A/M point mutation was the most common alteration (4 of 36 patients) within a prospectively collected cohort of 299 bladder cancer patients sequenced at our institution. We infected the ERCC2 wild-type KU19-19 bladder cancer cell line with a CRISPR/Cas9 lentivirus targeting residues 481-487 of ERCC2 and identified a cell clone harboring an ERCC2 in-frame deletion (M483_T484del). Following exposure to cisplatin and IR, cell viability was examined using Cell-titer Glo and clonogenic assays. Apoptosis was gauged by subG1 cell fraction measurement by flow cytometry. Results: ERCC2 mutant cells exhibited significantly increased cisplatin sensitivity compared to parental cells (IC50 0.3uM vs 2.0uM, p < 0.0001). Cisplatin treatment after 48 hours resulted in increased apoptosis in ERCC2 mutant vs parental cells (sub-G1 fraction 52% vs 16%, p = 0.01). ERCC2 mutant cells were more sensitive to combined IR (2 Gy) and cisplatin (1uM) compared to parental cells (SF2Gy (surviving fraction) 17 % vs 60%). Conclusions: ERCC2 mutations enhance cisplatin and IR sensitivity in a bladder cancer cell line model. ERCC2 alterations are likely the genetic basis for extraordinary response to cisplatin chemotherapy and IR in MIBC patients. Prospective genetic sequencing may help select ERCC2 mutant MIBC patients who are most likely to respond to chemotherapy or trimodality bladder-sparing therapy.

scholarly journals Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1607
Author(s):  
Ana T. P. C. Gomes ◽  
Rosa Fernandes ◽  
Carlos F. Ribeiro ◽  
João P. C. Tomé ◽  
Maria G. P. M. S. Neves ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Heck Reaction ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Porphyrin Derivatives ◽  
Biological Studies ◽  
Bladder Cancer Cells ◽  
Photodynamic Activity

Novel triazole-porphyrin derivatives (TZ-PORs) were synthesized through the Heck reaction and then incorporated into polyvinylpyrrolidone (PVP) micelles. After verifying that this incorporation did not compromise the photophysical and chemical features of TZ-PORs as photosensitizers, the phototoxicity of the formulations towards cancer cells was screened. Biological studies show high photodynamic activity of all PVP-TZ-POR formulations against a bladder cancer cell line with a particular highlight to PVP-TZ-POR 7e and 7f that are able to significantly reduce HT-1376 cell viability, while they had no effect on control ARPE-19 cells.

scholarly journals Effects of the Zinc Finger Protein 485 (ZNF485) on the Proliferation, Metastasis and Invasion of Bladder Cancer Cells

2021 ◽  
pp. 1-8
Author(s):  
Dabing Huang ◽  
Yiao Tan ◽  
Fangfang Zhao ◽  
Chunbao Zang ◽  
Shuhan Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Finger Protein ◽  
Bladder Cancer Cells ◽  
New Gene

Objectives: Bladder cancer is the second most common urological cancer worldwide with low early diagnosis and high mortality. The limited progress on the diagnostics and treatment largely impedes the survival of bladder cancer patients. Methods: Potential therapeutic biomarkers are urgently needed for future clinic treatment. We performed the RNA-seq assays and identified a new gene zinc finger protein 485, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients. Results: We found that inhibition of ZNF485 in bladder cancer cell line T24 and 5637 can obviously inhibit the proliferation and promotes the apoptosis of cancer cells. Furthermore, the wound healing and invasion assays showed that down-regulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-siRNA transfected obviously inhibited tumor growth in nude mice. Conclusion: Taken together, the results provide evidence that ZNF485 is involved in the tumorigenesis of bladder cancer, which might be a potential therapeutic biomarker for the treatment of this disease.

scholarly journals Targeting S1PR1 May Result in Enhanced Migration of Cancer Cells in Bladder Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4474
Author(s):  
Chin-Li Chen ◽  
En Meng ◽  
Sheng-Tang Wu ◽  
Hsing-Fan Lai ◽  
Yi-Shan Lu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Immune Cell ◽  
Underlying Mechanism ◽  
Relative Distribution ◽  
Bladder Tumors ◽  
Normal Tissues ◽  
Clinical Databases ◽  
Bladder Cancer Cells ◽  
Patient Prognosis

Clinical bladder tumor histological analysis shows that high expression of S1PR1 is associated with poor patient prognosis. However, there are no studies that describe the underlying mechanism. To investigate the relative distribution and actual function of S1PR1 in bladder tumors, we analyzed multiple clinical databases in combination with tumor purity and immune cell infiltration simulations, as well as databases of well-defined histological phenotypes of bladder cancer, and single-cell sequencing of adjacent normal tissues and bladder tumors, and further compared them with bladder cancer cell lines. The results showed that S1PR1 expression was generally higher in normal tissues than in bladder cancer tissues, and its distribution was mainly in endothelial cells or immune cells. The association between high S1PR1 expression and poor prognosis may be due to tumor invasion of adjacent normal tissues, where highly expressed S1PR1 may affect prognostic interpretation. The effect of S1PR1 itself on cancer cells was associated with cell adhesion, and in bladder cancer cells, S1PR1 expression was negatively correlated with cell motility. Moreover, the use of FTY-720 will cause an increased metastatic ability of bladder cancer cells. In conclusion, we suggest that the use of S1PR1-specific inhibition as a synergistic treatment requires more observation and consideration.

OVER EXPRESSION OF HYPOXIA-INDUCIBLE FACTOR-1α IN RENAL AND BLADDER CANCER CELLS INCREASES TUMORIGENIC POTENCY

2005 ◽  
Vol 173 (5) ◽  
pp. 1762-1766 ◽  
Author(s):  
YUKIHIRO KONDO ◽  
JUNKO HAMADA ◽  
CHIE KOBAYASHI ◽  
RYOSUKE NAKAMURA ◽  
YASUTOMO SUZUKI ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Over Expression ◽  
Hypoxia Inducible Factor 1Α ◽  
Bladder Cancer Cells

Possibilities of in silico estimations for the development of pharmaceutical composition phytoladaptogene cytotoxic for bladder cancer cells

2021 ◽  
Vol 67 (3) ◽  
pp. 278-288
Author(s):  
N.S. Ionov ◽  
M.A. Baryshnikova ◽  
E.V. Bocharov ◽  
P.V. Pogodin ◽  
A.A. Lagunin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
In Silico ◽  
Caspase 3 ◽  
Bladder Cancer Cell Line ◽  
Wide Range ◽  
Bladder Cancer Cells ◽  
Pharmaceutical Composition

Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: — the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.

scholarly journals Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

2020 ◽  
Vol 21 (16) ◽  
pp. 5658
Author(s):  
Kyoung-Hwa Lee ◽  
Byung-Chan Kim ◽  
Seung-Hwan Jeong ◽  
Chang Wook Jeong ◽  
Ja Hyeon Ku ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Xenograft Model ◽  
Histone Demethylase ◽  
Bladder Cancer Cell ◽  
Bladder Cancer Cell Line ◽  
Mouse Xenograft Model ◽  
Bladder Cancer Cells

Histone demethylase KDM7A regulates many biological processes, including differentiation, development, and the growth of several cancer cells. Here, we have focused on the role of KDM7A in bladder cancer cells, especially under drug-resistant conditions. When the KDM7A gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown in the bladder cancer cells repressed the activity of androgen receptor (AR) through epigenetic regulation. When we developed a cisplatin-resistant bladder cancer cell line, we found that AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells, showed decreased cell proliferation. In the mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of the bladder tumor. We also observed the upregulation of KDM7A expression in patients with bladder cancer. The findings suggest that histone demethylase KDM7A mediates the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in patients with cisplatin-resistant bladder cancer.

scholarly journals A Microfluidic Detection System for Bladder Cancer Tumor Cells

Micromachines ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 871
Author(s):  
Shuxing Lv ◽  
Jinwei Yu ◽  
Yan Zhao ◽  
Hongxiang Li ◽  
Fang Zheng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Diagnosis ◽  
Detection System ◽  
Cell Number ◽  
Bladder Cancer Cell Line ◽  
Bladder Cancer Cells ◽  
Diluted Solution

The clinical characteristics of excreted tumor cells can be found in the urine of bladder cancer patients, meaning the identification of tumor cells in urine can assist in bladder cancer diagnosis. The presence of white blood cells and epithelial cells in the urine interferes with the recognition of tumor cells. In this paper, a technique for detecting cancer cells in urine based on microfluidics provides a novel approach to bladder cancer diagnosis. The bladder cancer cell line (T24) and MeT-5A were used as positive bladder tumor cells and non-tumor cells, respectively. The practicality of the tumor cell detection system based on microfluidic cell chip detection technology is discussed. The tumor cell (T24) concentration was around 1 × 104 to 300 × 104 cells/mL. When phosphate buffer saline (PBS) was the diluted solution, the tumor cell detected rate was 63–71% and the detection of tumor cell number stability (coefficient of variation, CV%) was 6.7–4.1%, while when urine was the diluted solution, the tumor cell detected rate was 64–72% and the detection of tumor cell number stability (CV%) was 6.3–3.9%. In addition, both PBS and urine are tumor cell dilution fluid solutions. The sample was analyzed at a speed of 750 microns per hour. Based on the above experiments, a system for detecting bladder cancer cells in urine by microfluidic analysis chip technology was reported. The rate of recognizing bladder cancer cells reached 68.4%, and the speed reached 2 mL/h.

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