Ailanthone inhibits cell growth and migration of cisplatin resistant bladder cancer cells through down-regulation of Nrf2, YAP, and c-Myc expression.

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5 µM) alone or in combination. Cell growth, proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins were evaluated. siRNA blockade was used to investigate the functional impact of the proteins. Short-term application of SFN and/or everolimus resulted in significant tumor growth suppression, with additive inhibition on clonogenic tumor growth. Long-term everolimus treatment resulted in resistance development characterized by continued growth, and was associated with elevated Akt-mTOR signaling and cyclin-dependent kinase (CDK)1 phosphorylation and down-regulation of p19 and p27. In contrast, SFN alone or SFN+everolimus reduced cell growth and proliferation. Akt and Rictor signaling remained low, and p19 and p27 expressions were high under combined drug treatment. Long-term exposure to SFN+everolimus also induced acetylation of the H3 and H4 histones. Phosphorylation of CDK1 was diminished, whereby down-regulation of CDK1 and its binding partner, Cyclin B, inhibited tumor growth. In conclusion, the addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

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Retraction: “Down-regulation of uPA and uPAR by 3,3′-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells” by Ahmad et al.

Journal of Cellular Biochemistry ◽

10.1002/jcb.25583 ◽

2016 ◽

Vol 117 (8) ◽

pp. 1959-1959

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Down Regulation ◽

Cell Growth And Migration ◽

And Migration

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Changes in Tumor Growth and Metastatic Capacities of J82 Human Bladder Cancer Cells Suppressed by Down-Regulation of Calreticulin Expression

American Journal Of Pathology ◽

10.1016/j.ajpath.2011.05.015 ◽

2011 ◽

Vol 179 (3) ◽

pp. 1425-1433 ◽

Cited By ~ 26

Author(s):

Yi-Chien Lu ◽

Chiung-Nien Chen ◽

Bojeng Wang ◽

Wen-Ming Hsu ◽

Szu-Ta Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Human Bladder Cancer ◽

Down Regulation ◽

Human Bladder ◽

Bladder Cancer Cells ◽

Human Bladder Cancer Cells

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Down-regulation LncRNA-SNHG15 contributes to proliferation and invasion of bladder cancer cells

BMC Urology ◽

10.1186/s12894-021-00852-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Aldhabi Mokhtar ◽

Chuize Kong ◽

Zhe Zhang ◽

Yan Du

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Tumor Stage ◽

Rt Pcr ◽

Down Regulation ◽

Bladder Cancer Cells ◽

Cancer Tissues ◽

Proliferation And Invasion

Abstract Objectives The aim of this study was to investigate the effect of lncRNA-SNHG15 in bladder carcinoma using cell lines experiments and the relationship between clinical characteristics and lncRNA-SNHG15 expression was analyzed. Methods Bladder cancer tissues and near-cancer tissues were collected. The real-time PCR (RT-PCR) was used to detect the expression of lncRNA-SNHG15 in tissues and cell lines. The expression of lncRNA-SNHG15 was downregulated by interference (siRNA), as detected by RT-PCR, that was used to determine the efficiency of the interference. CCK-8 and Transwell assays were used to evaluate the effect of lncRNA-SNHG15 on the proliferation and invasion capability of bladder cancer cells. The t-test was used for Statistical analyses, which were carried out using the Statistical Graph pad 8.0.1.224 software. Result The expression of lncRNA-SNHG15 was up regulated in 5637, UMUC3 and T24 cell lines compared with corresponding normal controls (P < 0.05). Up regulation was positively related to tumor stage (P = 0.015). And tumor size (P = 0.0465). The down-regulation of lncRNA-SNHG15 with siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion. Conclusion This study showed that lncRNA-SNHG15 is overexpressed in bladder cancer tissues and (5637, UMUC3 T24) cell lines. Up regulation was positively related to tumor stage (P = 0.015), and tumor size (P = 0.0465). Down-regulation of lncRNA-SNHG15 by siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion, indicating a potential molecular target for future tumor targeted therapy.

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Down-regulation of autophagy-associated protein increased acquired radio-resistance bladder cancer cells sensitivity to taxol

International Journal of Radiation Biology ◽

10.1080/09553002.2021.1872812 ◽

2021 ◽

pp. 1-16

Author(s):

Xiangli Ma ◽

Guangmin Mao ◽

Rulve Chang ◽

Fang Wang ◽

Xiangyan Zhang ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Down Regulation ◽

Bladder Cancer Cells

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The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

Cellular Physiology and Biochemistry ◽

10.1159/000480419 ◽

2017 ◽

Vol 43 (1) ◽

pp. 405-418 ◽

Cited By ~ 46

Author(s):

Yaoyao Xiong ◽

Long Wang ◽

Yuan Li ◽

Minfeng Chen ◽

Wei He ◽

...

Keyword(s):

Bladder Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Cancer Growth ◽

Invasion And Migration ◽

Non Coding Rna ◽

Bladder Cancer Cells ◽

And Migration ◽

Cancer Tissues ◽

Long Non Coding Rna

Backgrounds/Aims: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

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Polyporus polysaccharide regulates proliferation, apoptosis and migration of bladder cancer cells by polarizing macrophages to M1 subtype in tumor microenvironment

10.21203/rs.3.rs-31455/v4 ◽

2020 ◽

Author(s):

Wenyu Jia ◽

Siwan Luo ◽

Gena Lai ◽

Shiqi Li ◽

Shuai Huo ◽

...

Keyword(s):

Flow Cytometry ◽

Bladder Cancer ◽

Western Blot ◽

Cancer Cells ◽

Activated Macrophages ◽

Tnf Α ◽

Bladder Cancer Cells ◽

And Migration ◽

Mesenchymal Transformation ◽

M1 Type

Abstract BackgroundPolyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of PPS activated macrophages in the treatment of bladder cancer.Methods100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Flow cytometry was used to detect the expression of CD14 and CD68 to verify the establishment of macrophage model. After that, Macrophages derived from THP-1 were treated with different concentrations of PPS (1,10 and 100 ug/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with PPS. The conditioned medium from PPS-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2¢-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein.ResultsPPS promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. The results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial–mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. ConclusionThe findings indicated that PPS inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.

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