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吲哚-3-甲醇环状四聚体衍生物 CTet 与顺铂和多柔比星在三阴性乳腺癌细胞系中协同作用。

The Indole-3-carbinol cyclic tetrameric derivative CTet synergizes with cisplatin and doxorubicin in triple-negative breast cancer cell lines.

机构信息

Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Via Saffi 2, 61029 Urbino (PU), Italy.

出版信息

Anticancer Res. 2013 May;33(5):1867-72.

Abstract

BACKGROUND/AIM: The indole-3-carbinol cyclic tetrameric derivative (CTet) inhibits breast cancer cell proliferation by endoplasmic reticulum stress and autophagy-related cell death induction, AKT/PKB (protein kinase B) activity inhibition and p53-independent overexpression of cyclin-dependent kinase inhibitor-1A (p21/CDKN1A). In the present study we evaluated the synergistic activity of CTet in combination with cisplatin and doxorubicin in triple-negative breast cancer cell lines.

MATERIALS AND METHODS

Synergisms were evaluated in terms of cell viability, induction of autophagy and overexpression of microtubule-associated protein-1 light chain-3 beta (MAP1LC3B) autophagy-related gene in MDA-MB-231 and BT-20 triple-negative breast cancer cells.

RESULTS

We demonstrated that CTet in combination with both cisplatin and doxorubicin synergistically inhibits cell viability and induces autophay. The MAP1LC3B gene was synergistically overexpressed in MDA-MB-231 cells treated with CTet-cisplatin combination. Moreover, the cytotoxic activity of CTet was improved in cells pre-treated with cisplatin and doxorubicin.

CONCLUSION

This preliminary in vitro study confirms the potential of CTet as a chemopreventive agent or chemotherapeutic in combination with standard approaches for triple-negative breast cancer.

摘要

背景/目的:吲哚-3-甲醇环状四聚体衍生物(CTet)通过内质网应激和自噬相关细胞死亡诱导、AKT/PKB(蛋白激酶 B)活性抑制以及 p53 非依赖性细胞周期蛋白依赖性激酶抑制剂 1A(p21/CDKN1A)过表达来抑制乳腺癌细胞增殖。在本研究中,我们评估了 CTet 与顺铂和多柔比星联合应用于三阴性乳腺癌细胞系的协同活性。

材料和方法

通过细胞活力、自噬诱导和微管相关蛋白 1 轻链 3β(MAP1LC3B)自噬相关基因的过表达来评估 MDA-MB-231 和 BT-20 三阴性乳腺癌细胞中的协同作用。

结果

我们证明 CTet 与顺铂和多柔比星联合使用可协同抑制细胞活力并诱导自噬。在 CTet-顺铂联合处理的 MDA-MB-231 细胞中,MAP1LC3B 基因协同过表达。此外,在先用顺铂和多柔比星预处理的细胞中,CTet 的细胞毒性活性得到改善。

结论

这项初步的体外研究证实了 CTet 作为一种化学预防剂或化疗药物与标准的三阴性乳腺癌治疗方法联合应用的潜力。

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