Astemizole promotes the anti-tumor effect of vitamin D through inhibiting miR-125a-5p-meidated regulation of VDR in HCC

Xu, Junli; Wang, Yan; Zhang, Ya; Dang, Shan; He, Shuixiang

doi:10.1016/j.biopha.2018.08.153

Cited by 27 publications

(16 citation statements)

References 33 publications

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“…Among several possible microRNAs that potentially interact with the VDR 3′UTR sequence, we selected hsa-miR-125a-5p, hsa-miR-125b-5p and hsa-miR-214-3p for analysis. In the case of all these miRNAs, we found significant differences in their expression between the investigated tissues (Supplementary Figure S1 and Kurylowicz et al, 2016 and 2017 [19,20]) and their role in the regulation of VDR expression was confirmed by in vitro studies [15,21,22].…”

Section: Resultssupporting

confidence: 66%

“…We found significant, negative correlations between VDR mRNA level and levels of hsa-miR-125a-5p, hsa-miR-125b-5p, and hsa-miR-214-3p in VAT of obese subjects. All these miRNAs were found to participate in the regulation of VDR expression in vitro [15,21,22], and their expression is decreased in visceral adipose tissue in obesity [19,20]. We do not observe similar correlations in SAT of obese individuals.…”

Section: Discussioncontrasting

confidence: 69%

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Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level

Jonas

Kuryłowicz

Bartoszewicz

et al. 2019

IJMS

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Background: Given the role that vitamin D (VD) plays in the regulation of the inflammatory activity of adipocytes, we aimed to assess whether obesity changes the expression of VD-related genes in adipose tissue and, if so, to investigate whether this phenomenon depends on microRNA interference and how it may influence the local inflammatory milieu. Methods: The expression of genes encoding VD 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and receptor (VDR), selected interleukins and microRNAs was evaluated by real-time PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of 55 obese (BMI > 40 kg/m2) and 31 normal-weight (BMI 20–24.9 kg/m2) individuals. Results: VDR mRNA levels were higher, while CYP27B1 levels were lower in adipose tissues of obese patients than in those of normal-weight controls (VAT: P = 0.04, SAT: P < 0.0001 and VAT: P = 0.004, SAT: P = 0.016, respectively). The expression of VDR in VAT of obese subjects correlated negatively with levels of miR-125a-5p (P = 0.0006, rs = −0.525), miR-125b-5p (P = 0.001, rs = −0.495), and miR-214-3p (P = 0.009, rs = −0.379). Additionally, VDR mRNA concentrations in visceral adipose tissues of obese subjects correlated positively with mRNA levels of interleukins: 1β, 6 and 8. Conclusions: We observed obesity-associated up-regulation of VDR and down-regulation of CYP27B mRNA levels in adipose tissue. VDR expression correlates with the expression of pro-inflammatory cytokines and may be regulated by miRNAs.

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Section: Resultssupporting

confidence: 66%

Section: Discussioncontrasting

confidence: 69%

Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level

Jonas

Kuryłowicz

Bartoszewicz

et al. 2019

IJMS

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“…In the former studies [ 26 , 27 ], the anti-tumor effects are usually played by inducing apoptosis of tumor cells, however, the atorvastatin triggered inhibition of apoptosis in this study. Moreover, atorvastatin administration also increased Bcl-2 expression in PCa cells, which seems to be controversial to the anti-tumor effects comparing with previous study [ 28 ].…”

Section: Discussionmentioning

confidence: 64%

Atorvastatin Enhances Effects of Radiotherapy on Prostate Cancer Cells and Xenograft Tumor Mice Through Triggering Interaction Between Bcl-2 and MSH2

Yuan

Shen

et al. 2020

Med Sci Monit

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Background Prostate cancer (PCa) is considered to be the 4 th most common cancer in males in the world. This study aimed to explore effects of atorvastatin on colony formation of PCa cells and radio-resistance of xenograft tumor models. Material/Methods PCa cell lines, including PC3, DU145, and Lncap, were treated with irradiation (4 Gy) and/or atorvastatin (6 μg/mL). Cells were divided into tumor cell group, irradiation treatment group (IR group) and irradiation+atorvastatin treatment group (IR-AS group). Xenograft tumor mouse model was established. Plate clone formation assay (multi-target/single-hit model) was conducted to evaluate colony formation. Flow cytometry analysis was employed to detect apoptosis. Interaction between Bcl-2 and MSH2 was evaluated with immuno-fluorescence assay. Results According to the plate colony formation assay and multi-target/single-hit model, IR-treatment significantly suppressed colony formation in PCa cells (including PC3, DU145, and Lncap cells) compared to no-IR treated cells ( P <0.05). Atorvastatin remarkably enhanced inhibitive effects of irradiation on colony formation of PCa cells ( P <0.05), however, the IR+AS group demonstrated no effects on apoptosis, comparing to IR group ( P >0.05). Atorvastatin administration (IR+AS group) significantly reduced tumor size of IR-treated PCa cells-induced xenograft tumor mice ( P <0.05). Bcl-2 interacted with MSH2 both in tumor tissues of xenograft tumor mice. Conclusions Atorvastatin administration inhibited colony formation in PCa cells and enhanced effects of radiotherapy on tumor growth of xenograft tumor mice, which might be associated with interaction between Bcl-2 and MSH2 molecule.

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“…They also clarified that this combination inhibits the tumor suppressor miR-125a-5p and is responsible for subsequent upregulation of the VD receptor. These outcomes highlight the crucial role of combined treatment of astemizole and VD for the cure of hepatocellular carcinoma cells [69]. Similarly, in other studies, VD was encapsulated into nanostructured lipid carriers and was used as an adjuvant to elevate the efficacy of doxorubicin on concurrent administration in breast cancer treatment.…”

Section: Drug Delivery Systems For the Prevention And Treatment Ofmentioning

confidence: 86%

Drug Delivery Systems for Vitamin D Supplementation and Therapy

2019

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Vitamin D (VD) is a fat-soluble prohormone well known for its role in regulating calcium and phosphate metabolism. It has been clinically used for many years to prevent rickets in children, osteomalacia, and osteoporosis in adults. VD insufficiency is a common medical condition, and many supplements are available in the market in order to increase serum 25-hydroxy VD levels to recommended amounts. Over the course of the last decades, it has become increasingly clear that calcitriol, an active form of VD, regulates multiple cellular processes with effects on normal and malignant cell growth and differentiation, and on the immune and cardiovascular function. Increasing evidence supports the role of the VD system in cancer prevention and therapy. Due to many pleiotropic and beneficial effects in extra-skeletal disorders, VD has gained potential and become an interesting active for encapsulation into drug delivery systems. The purpose of this review is to present the diversity of drug delivery systems that have been reported for VD or VD derivatives in an orderly manner across the following categories: Oral administration, application on the skin, cancer prevention/therapy, and other diseases or routes of administration.

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Astemizole promotes the anti-tumor effect of vitamin D through inhibiting miR-125a-5p-meidated regulation of VDR in HCC

Cited by 27 publications

References 33 publications

Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level

Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level

Atorvastatin Enhances Effects of Radiotherapy on Prostate Cancer Cells and Xenograft Tumor Mice Through Triggering Interaction Between Bcl-2 and MSH2

Drug Delivery Systems for Vitamin D Supplementation and Therapy

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