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联合 Dkk-3 和 5-ALA 介导的光动力疗法对乳腺癌细胞集落的抗肿瘤作用。

Antitumor effect of combined Dkk-3 and 5-ALA mediated photodynamic therapy in breast cancer cell's colony.

机构信息

Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Periodontology Department, AJA University of Medical Sciences, Tehran, Iran; Laser Research Center in Medical Sciences, AJA University of Medical Sciences, Tehran, Iran.

出版信息

Photodiagnosis Photodyn Ther. 2016 Jun;14:200-3. doi: 10.1016/j.pdpdt.2016.04.001. Epub 2016 Apr 9.

Abstract

BACKGROUND

Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member that efficiently suppresses tumor growth in several types of cancer. Photodynamic therapy (PDT) is commonly used for treatment of different types of cancer and antitumor efficacy of PDT increased upon Wnt signaling inhibition. The objective of this study is to evaluate the effects of Dkk-3 and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer cell line.

MATERIAL AND METHODS

4T1 breast cell line were treated with either Dkk-3 (20, 40 and 80ng/ml) 24h followed by 5-ALA-PDT (1, 3 and 6J/cm2). Also, 5-ALA was used at dose 1mM. The apoptosis and post apoptotic necrosis were evaluated by FITC-Annexin-PI apoptosis detection kit.

RESULTS

Obtained findings showed that both Dkk-3 and ALA-PDT have cytotoxic effects on cancer cells in a dose-dependent manner. The subtracted mean of death cell percentage in 20, 40 and 80ng/ml of Dkk-3 were 6.8±0.7%, 10.4±0.84% and 16.1±1.55% respectively. The subtracted mean of cell death induction in 5-ALA mediated PDT was 5.3±0.77% at 6J/cm2. Dkk-3 with ALA-PDT significantly increased cell death compared to either Dkk-3 or 5-ALA mediated PDT in cancer 4T1 cancer cell line (P˂0.001).

CONCLUSION

In this study, observed results revealed that Dkk-3 induced the apoptosis in 4T1 breast cancer cells and apoptotic effects of Dkk-3 intensified following photodynamic therapy. This study provided a novel insight into the development of therapeutic strategies for treatment of breast cancer using Dkk-3 combined with PDT.

摘要

背景

Dickkopf 3(Dkk-3)是一种 Wnt 信号抑制剂,是一种特征性的 DKK 家族成员,能有效抑制多种类型癌症的肿瘤生长。光动力疗法(PDT)常用于治疗不同类型的癌症,并且 Wnt 信号抑制可增加 PDT 的抗肿瘤疗效。本研究旨在评估 Dkk-3 和 5-氨基酮戊酸(5-ALA)介导的光动力疗法对乳腺癌细胞系的影响。

材料和方法

用 Dkk-3(20、40 和 80ng/ml)处理 4T1 乳腺癌细胞 24 小时,然后进行 5-ALA-PDT(1、3 和 6J/cm2)。同时,使用 1mM 的 5-ALA。用 FITC-Annexin-PI 凋亡检测试剂盒评估细胞凋亡和凋亡后坏死。

结果

研究结果表明,Dkk-3 和 ALA-PDT 均以剂量依赖性方式对癌细胞具有细胞毒性作用。20、40 和 80ng/ml Dkk-3 的死亡细胞百分比平均值分别为 6.8±0.7%、10.4±0.84%和 16.1±1.55%。在 6J/cm2 的 5-ALA 介导的 PDT 中,细胞死亡诱导的平均值为 5.3±0.77%。与 Dkk-3 或 5-ALA 介导的 PDT 相比,Dkk-3 联合 ALA-PDT 显著增加了癌细胞 4T1 的细胞死亡(P˂0.001)。

结论

在这项研究中,观察到的结果表明,Dkk-3 诱导了 4T1 乳腺癌细胞的凋亡,并且 Dkk-3 后的光动力疗法增强了凋亡作用。本研究为开发使用 Dkk-3 联合 PDT 治疗乳腺癌的治疗策略提供了新的见解。

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