维生素D3和5-aza-2 ' -脱氧胞苷对VDR甲基化和乳腺癌进展的协同作用

IF 0.3 Q4 OBSTETRICS & GYNECOLOGY
Anjali K. Ravi , Saradhadevi Muthukrishnan , S. Abirami , Gayathiri Gunasangkaran , Vijaya Anand Arumugam , Velayuthaprabhu Shanmugam , Marie Arockianathan Pushpam , Ashokkumar Kaliyaperumal
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引用次数: 0

摘要

乳腺癌(BC)是一种高度侵袭性的疾病,治疗选择有限。骨化三醇是维生素D3的活性形式,通过维生素D受体(VDR)发挥抗癌作用,但其功效往往因VDR启动子超甲基化而降低。本研究探讨了VDR启动子超甲基化在乳腺癌中的作用,并评估了5-Aza-2dC和维生素D3在恢复VDR功能和提高治疗效果方面的潜力。方法采用DMBA诱导balb /c小鼠VDR启动子超甲基化。评估5-Aza-2dC和维生素D3对VDR、CYP27B1和CYP24A1表达的影响,以评估它们对骨化三醇信号传导和BC增殖的影响。结果dba处理小鼠VDR超甲基化,CYP24A1表达升高,VDR和CYP27B1表达降低,肿瘤生长明显增强。5-Aza-2dC治疗逆转了VDR超甲基化,恢复了VDR和CYP27B1的表达,抑制了CYP24A1,导致肿瘤大小减小,维生素D3水平升高。维生素D3预处理可保持VDR和CYP27B1的表达,降低CYP24A1,抑制VDR甲基化,抑制肿瘤增殖。5-Aza-2dC和维生素D3联合治疗可协同增强VDR去甲基化,降低CYP24A1,增加维生素D3水平,并显著抑制BC增殖,减小肿瘤大小。结论用5-Aza-2dC和维生素D3逆转VDR高甲基化是克服骨化三醇耐药和改善BC治疗结果的有希望的策略。这种组合可能会提高以维生素d3为基础的治疗BC的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Synergistic effects of vitamin D3 and 5-aza-2′-deoxycytidine on VDR methylation and breast cancer progression

Synergistic effects of vitamin D3 and 5-aza-2′-deoxycytidine on VDR methylation and breast cancer progression

Introduction

Breast cancer (BC) is a highly aggressive disease with limited treatment options. Calcitriol, the active form of vitamin D3, exerts anticancer effects via the vitamin D receptor (VDR), but its efficacy is often reduced by VDR promoter hypermethylation. This study investigates the role of VDR promoter hypermethylation in breast cancer and evaluates the potential of 5-Aza-2dC and vitamin D3 to restore VDR function and enhance therapeutic efficacy.

Methods

BALB/c mice were treated with DMBA to induce VDR promoter hypermethylation. The effects of 5-Aza-2dC and Vitamin D3 on VDR, CYP27B1, and CYP24A1 expression were evaluated to assess their impact on calcitriol signaling and BC proliferation.

Results

DMBA-treated mice exhibited VDR hypermethylation, increased CYP24A1, and decreased VDR and CYP27B1 expression, with significantly enhanced tumor growth. Treatment with 5-Aza-2dC reversed VDR hypermethylation, restored VDR and CYP27B1 expression, and suppressed CYP24A1, leading to reduced tumor size and higher vitamin D3 levels. Vitamin D3 pre-treatment preserved VDR and CYP27B1 expression, reduced CYP24A1, and protected against VDR methylation, decreasing tumor proliferation. Combined treatment with 5-Aza-2dC and vitamin D3 synergistically enhanced VDR demethylation, reduced CYP24A1, increased vitamin D3 levels, and significantly inhibited BC proliferation, reducing tumor size.

Conclusion

Reversing VDR hypermethylation with 5-Aza-2dC and vitamin D3 offers a promising strategy to overcome calcitriol resistance and improve therapeutic outcomes in BC. This combination may enhance the efficacy of vitamin D3-based therapies in BC treatment.
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来源期刊
Revista de Senologia y Patologia Mamaria
Revista de Senologia y Patologia Mamaria Medicine-Obstetrics and Gynecology
CiteScore
0.30
自引率
0.00%
发文量
74
审稿时长
63 days
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