scholarly journals Hyperbaric Oxygen Enhanced Mitochondria-Targeted Chemotherapy in Bladder Cancer

2020 ◽  
Author(s):  
Chongxing Shen ◽  
Xiaofeng Yue ◽  
Linyong Dai ◽  
Jianwu Wang ◽  
Jinjin Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Hyperbaric Oxygen ◽  
Cell Uptake ◽  
Bladder Cancer Cells ◽  
First Time ◽  
Mitochondria Targeting

Abstract Background: Bladder cancer has a high rate of recurrence and drug resistance due to a lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types. In the study, we aimed to investigate the anti-tumor effect of IR-780 combined with hyperbaric oxygen (HBO) on bladder cancer.Methods: Using in vitro cell line data, in vivo model data and clinical data, we tested the ability of IR-780 to selectively accumulate in bladder cancer. We also evaluated the anti-tumor effect of IR-780 combined or not with HBO both in vitro and in vivo, and explored the potential mechanism of its anti-tumor effect. Results: We revealed for the first time that IR-780 selectively accumulated in bladder cancer (bladder cancer cells, xenografts and bladder cancer samples from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. Further study displayed that the combination with HBO could significantly enhance the antitumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial reactive oxygen species (ROS) production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusions: These data identify for the first time a combination of IR-780 and HBO (IR-780+HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

scholarly journals The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinan Guo ◽  
Zhixin Chen ◽  
Hongtao Jiang ◽  
Zhou Yu ◽  
Junming Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Bladder Cancer Cell ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Abstract Background Bladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression. Methods Gene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model. Results Our results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues. Conclusion Collectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Positive Association ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background: The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer.Methods: This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry.Results: ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion: This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer 

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Positive Association ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background: The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer.Methods: This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry.Results: ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion: This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
W. Wang ◽  
J. Qiu ◽  
P. Qu ◽  
H. Chen ◽  
J. Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Positive Association ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer. Methods This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry. Results ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

scholarly journals Regulator of Cullins-1 (ROC1) Negatively Regulates the Gli2 Regulator SUFU to Activate the Hedgehog Pathway in Bladder Cancer

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Malignant Progression ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background: The regulator of cullins-1 (ROC1) is an essential subunit in the Cullin-RING ligase (CRL) protein complex and was shown to be critical in bladder cancer cell survival and malignant progression. This study aimed to explore the regulatory mechanism of ROC1 in bladder cancer malignant progression. Methods: This study explored the underlying mechanisms using both in vitro and in vivo experiments. The expression of the components of Sonic Hedgehog (SHH) pathway was determined by western blotting analysis. ROC1 expression in human tumours was evaluated by immunohistochemical analysis. Results: The data showed that ROC1 overexpression promoted growth of bladder cancer cells, whereas knockdown of ROC1 expression had an opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target SUFU for ubiquitin-dependent degradation, allowing the Gli2 release from the SUFU complex to activate SHH pathway. Furthermore, knockdown of SUFU expression partially rescue the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. At ex vivo, tissue microarray analysis of human bladder cancer specimens revealed an positive association of ROC1 expression with the SHH pathway activity. Conclusion: The current study demonstrated the dysregulation of ROC1-SUFU-GLI2 axis played an important role in bladder cancer progression and targeting of ROC1 expression is warranted further investigation as a novel strategy for future control of bladder cancer.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Malignant Progression ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background The regulator of cullins-1 (ROC1) is an essential subunit in the Cullin-RING ligase (CRL) protein complex and was shown to be critical in bladder cancer cell survival and malignant progression. This study aimed to explore the regulatory mechanism of ROC1 in bladder cancer malignant progression. Methods This study explored the underlying mechanisms using both in vitro and in vivo experiments. The expression of the components of Sonic Hedgehog (SHH) pathway was determined by western blotting analysis. ROC1 expression in human tumours was evaluated by immunohistochemical analysis. Results The data showed that ROC1 overexpression promoted growth of bladder cancer cells, whereas knockdown of ROC1 expression had an opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target SUFU for ubiquitin-dependent degradation, allowing the Gli2 release from the SUFU complex to activate SHH pathway. Furthermore, knockdown of SUFU expression partially rescue the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. At ex vivo, tissue microarray analysis of human bladder cancer specimens revealed an positive association of ROC1 expression with the SHH pathway activity. Conclusion The current study demonstrated the dysregulation of ROC1-SUFU-GLI2 axis played an important role in bladder cancer progression and targeting of ROC1 expression is warranted further investigation as a novel strategy for future control of bladder cancer.

ENHANCED SENSITIVITY OF BLADDER CANCER CELLS TO CISPLATIN MEDIATED CYTOTOXICITY AND APOPTOSIS IN VITRO AND IN VIVO BY THE SELECTIVE CYCLOOXYGENASE-2 INHIBITOR JTE-522

2004 ◽  
Vol 172 (4 Part 1) ◽  
pp. 1474-1479 ◽  
Author(s):  
YOICHI MIZUTANI ◽  
HIROYUKI NAKANISHI ◽  
YONG NAN LI ◽  
NODOKA SATO ◽  
AKIHIRO KAWAUCHI ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cyclooxygenase 2 ◽  
Enhanced Sensitivity ◽  
Bladder Cancer Cells

scholarly journals DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chin-Hui Lai ◽  
Kexin Xu ◽  
Jianhua Zhou ◽  
Mingrui Wang ◽  
Weiyu Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Tumor Grade ◽  
In Vivo Studies ◽  
Mechanistic Study ◽  
Tumor Promotor ◽  
Bladder Cancer Cells

AbstractBladder cancer is one of the most commonly diagnosed malignant tumors in the urinary system and causes a massive cancer-related death. DEPDC1B is a DEP domain-containing protein that has been found to be associated with a variety of human cancers. This study aimed to explore the role and mechanism of DEPDC1B in the development of bladder cancer. The analysis of clinical specimens revealed the upregulated expression of DEPDC1B in bladder cancer, which was positively related to tumor grade. In vitro and in vivo studies showed that DEPDC1B knockdown could inhibit the growth of bladder cancer cells or xenografts in mice. The suppression of bladder cancer by DEPDC1B was executed through inhibiting cell proliferation, cell migration, and promoting cell apoptosis. Moreover, a mechanistic study found that SHC1 may be an important route through which DEPDC1B regulates the development of bladder cancer. Knockdown of SHC1 in DEPDC1B-overexpressed cancer cells could abolish the promotion effects induced by DEPDC1B. In conclusion, DEPDC1B was identified as a key regulator in the development of bladder cancer, which may be used as a potential therapeutic target in the treatment of bladder cancer.

In vitro and in vivo effects of HAL on porphyrin production in rat bladder cancer cells (AY27)

2019 ◽  
Vol 23 (07n08) ◽  
pp. 813-820
Author(s):  
Odrun A. Gederaas ◽  
Harald Husebye ◽  
Anders Johnsson ◽  
Susan Callaghan ◽  
Anders Brunsvik
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Active Agent ◽  
Laser Scanning Microscopy ◽  
Rat Bladder ◽  
Bladder Cancer Cells

Aminolevulinic acid and hexyl-aminolevulinate serve as biological precursors to produce photosensitive porphyrins in cells via the heme biosynthetic pathway. This pathway is integral to porphyrin-based photodynamic diagnosis and therapy. By adding exogenous hexyl-aminolevulinate to rat bladder cancer cells (AY27, in vitro) and an animal bladder cancer model (in vivo), fluorescent endogenous porphyrin production was stimulated. Lipophilic protoporphyrin IX was identified as the dominant species by reverse high-pressure liquid chromatography. Subcellular porphyrin localization in the AY27 cells was evaluated by confocal laser scanning microscopy and showed almost quantitative bleaching after 20 s. From this study, we ascertained that the protocol described herein is suitable for hexyl-aminolevulinate-mediated photodynamic therapy and diagnosis when protoporphyrin IX is the active agent.

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