BCL2 genotypes and prostate cancer survival

Renner, Wilfried; Langsenlehner, Uwe; Krenn-Pilko, S.; Eder, Petra; Langsenlehner, Tanja

doi:10.1007/s00066-017-1126-9

Cited by 19 publications

(11 citation statements)

References 27 publications

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“…Apoptosis and necrosis have been linked to the development and progression of various cancers, and are therapeutic targets for various cancers ( Thompson et al, 1995 ; Feng et al, 2016 ; Renner et al, 2017 ). Receptor interacting protein 1 (RIP1) kinase is a crucial regulator of cell survival and cell death, and is emerging as an important regulator of the cell fate in response to cellular stress ( Luan et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Wang

Zhu

et al. 2018

Front. Pharmacol.

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Objective: The purpose of this study was to evaluate the anticancer effects of Ophiopogonin D′ (OPD′, a natural product extracted from a traditional Chinese medicine (Radix Ophiopogonis) against androgen-independent prostate cancer cells and to explore the underlying molecular mechanism(s) of action.Methods: The CCK-8 assay was used to assess the viability of prostate cancer cells. The cell morphology was examined by an ultrastructural analysis via transmission electron microscopy. Cells in apoptosis (early and late stages) were detected using an Annexin V-FITC/propidium iodide kit with a FACSCaliber flow cytometer. JC-1, a cationic lipophilic probe, was employed to measure the mitochondrial membrane potential (MMP) of PC3 cells. Changes in the protein expression of RIPK1, C-RIPK1, caspase 8, cleaved-caspase 8, Bim, Bid, caspase 10, and cleaved-caspase 10 were evaluated by Western blotting. The mRNA expression of Bim was examined by quantitative real-time reverse transcription polymerase chain reaction. Z-VAD-FMK (a caspase inhibitor) and necrostatin-1 (a specific inhibitor of RIPK1) were utilized to determine whether the cell death was mediated by RIPK1 or caspases. PC3 and DU145 xenograft models in BALB/c nude mice were used to evaluate the anticancer activity of OPD′ in vivo.Results: OPD′ was shown to exert potent anti-tumor activity against PC3 cells. It induced apoptosis via a RIPK1-related pathway, increased the protein expression levels of RIPK1 and Bim, and decreased the levels of cleaved-RIPK1, caspase 8, cleaved-caspase 8, Bid, caspase 10, and cleaved-caspase 10. OPD′ also increased the mRNA expression of Bim. The protein expression of Bim was decreased when cells were pre-treated with necrostatin-1. Treatment with OPD′ inhibited the growth of PC3 and DU145 xenograft tumors in BALB/c nude mice.Conclusion: OPD′ significantly inhibited the in vitro and in vivo growth of prostate cells via RIPK1, suggesting that OPD′ may be developed as a potential anti-prostate cancer agent.

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Section: Introductionmentioning

confidence: 99%

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Wang

Zhu

et al. 2018

Front. Pharmacol.

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“…hsa-miR-575 and the hsa-miR-630 are proposed oncomiRNAs in other tumors such as gastric cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, and breast cancer [34][35][36][37][38][39][40]. hsa-miR-630 has different gene targets such as BCL-2, MTDH, YAP-1, SNAI2 [37][38][39] involved in PCa oncogenesis [41][42][43][44]. hsa-miR-575 has as a target BLID (BH3-like motif containing, BRCC2).…”

Section: Discussionmentioning

confidence: 99%

microRNA Expression Profiling in Young Prostate Cancer Patients

et al. 2020

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MicroRNAs (miRNAs) are small, non-coding RNA molecules with multiple roles in many biological processes. Few studies have shown the molecular characteristics in younger prostate cancer (PCa) patients. In this study, we performed miRNA profiling in young PCa (EO-PCa) cases compared with PCa arising in older men (LO-PCa). Experimental Design: Formalin-fixed, paraffin embedded tissue was used. miRNA was extracted for PCR array and NanoString methods. Relative miRNAs expression levels were obtained by comparing young vs older men, and young PCa tumor samples vs normal epithelium. Results: miRNA profiling showed a different expression pattern in PCa arising in younger men, and young PCa tumoral and its normal counterpart. Nine miRNAs showed differences in the expression compared to LO-PCa. Fourteen miRNAs were significantly up-regulated young PCa tumoral tissue compared to normal counterpart. The higher expression of miR-600 and miR-137 were associated with high Gleason score, extraprostatic extension and lymphatic invasion. Conclusion: These results suggest that PCa in younger patients has a different expression profile compared to normal tissue and PCa arising in older man. Differentially expressed miRNAs provide insights of molecular mechanisms involve in this PCa subtype.

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“…В то же время существуют работы, указывающие, что BCL2 усиливает стимулирующее действие гипоксии на синтез VEGF в клетках аденокарциномы ПЖ [15]. В исследованиях in vivo при трансфекции BCL2 в опухолевые клетки путем генной инженерии тканевая экспрессия фактора неоангиогенеза VEGF повышалась, степень васкуляризации опухолевых клеток усиливалась [16]. Таким образом, VEGF, способствующий выживаемости эндотелиальных клеток, являлся косвенным антиапоптическим фактором для опухолевых клеток.…”

Section: таблица 1 динамика пса (нг/мл) в сыворотке крови после рпэ unclassified

Association of Expression of Nfkb1, Hif1, Vegfa, Vegfв, Bax, Bcl2 Genes With Biochemical Remediation in Patients With Localized Prostate Cancer

Bova

Максимов

2019

Issled. prakt. med. (Print)

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Aim. To identify the association of NFKB1, HIF1, VEGFA, VEGFB, BAX, BCL2 gene expression in prostate adenocarcinoma cells with biochemical recurrence of localized prostate cancer. Patients and methods. Three groups of patients were formed in the study – the main one, the comparison group and the control group. In patients with prostate cancer (PC) in the main group (n = 56) with biochemical recurrence (BR) for two years after radical surgery, as well as in 60 patients without BR (experimental group) by real-time PCR in prostate cancer tissue the expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2 was determined. The control group consisted of 55 patients in whom, when performing diagnostic punctures for benign prostate tumors, biopsy specimens were taken in healthy tissues. The age of patients in the three groups ranged from 57 to 74 years (median 63 years). When quantifying expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2, the difference in the values of reaction threshold cycles (Ct) fixed for the studied and reference genes was determined. The relative level (Expr) was the ratio of Ct medians for each gene in two compared groups of the studied three ones: in the main group to the indicator in the control group, in the experimental group to the indicator in the control group, and also between the main group and the experimental group. Results. A comparative analysis of gene expression in prostate cancer tissue in the main group compared with the experimental group showed a statistically significant increase (p < 0,05) in the relative index for the HIF1 gene (2,7 times), the VEGFA gene (2,4 times ) and the NFKB1 gene (2 times). Consequently, in patients with localized early recurrence prostate cancer, initially in the prostate tissue, a higher level of expression of the NFKB1, HIF1 and VEGFA genes was established. In the experimental group relative to the control group, the expression of the proapoptic gene BAX was 1,6 times higher (p < 0,05), and for the antiapoptic gene BCL2 no changes were detected (p = 0,09). Thus, in patients with localized prostate cancer in the absence of BR, after radical prostatectomy, an initial increase in the expression of the BAX gene promoted the activation of apoptosis. In patients with localized prostate cancer, subsequent biochemical recurrence initially in the tissue of prostate adenocarcinoma inhibition of apoptosis due to increased expression of the BCL2 gene was observed. Conclusion. Enhancement of NFKB1, VEGFA, HIF1 and BCL2 gene expression in prostate tissue is associated with the development of BR in patients with localized prostate cancer.

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BCL2 genotypes and prostate cancer survival

Cited by 19 publications

References 27 publications

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

microRNA Expression Profiling in Young Prostate Cancer Patients

Association of Expression of Nfkb1, Hif1, Vegfa, Vegfв, Bax, Bcl2 Genes With Biochemical Remediation in Patients With Localized Prostate Cancer

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