Mechanism underlying resveratrol's attenuation of paclitaxel cytotoxicity in human breast cancer cells: Role of the SIRT1-FOXO1-HER3 signaling pathway.
Mechanism underlying resveratrol's attenuation of paclitaxel cytotoxicity in human breast cancer cells: Role of the SIRT1-FOXO1-HER3 signaling pathway.
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白藜芦醇减弱人乳腺癌细胞紫杉醇细胞毒性的机制：SIRT1-FOXO1-HER3 信号通路的作用。
DOI：
10.1016/j.ctarc.2021.100386
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发表时间：
2021-01-01
影响因子：
--
通讯作者：
Zhu, Bao Ting
中科院分区：
文献类型：
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作者：
Fukui, Masayuki;Choi, Hye Joung;Zhu, Bao Ting
白藜芦醇（RES）是一种膳食酚类化合物，据报道具有癌症化学保护和化疗作用。此前我们意外地观察到RES在一些乳腺癌细胞中具有生长促进作用，并且可以降低MDA-MB-231和SKBR-3细胞对紫杉醇诱导的细胞死亡的敏感性，但在MCF-7细胞中没有观察到这种现象。本研究旨在确定RES减弱紫杉醇对癌细胞毒性的机制。发现RES仅在表达HER 3蛋白的人乳腺癌细胞中降低紫杉醇的抗癌作用。用RES处理SKBR-3细胞以剂量依赖性方式增加HER 3表达。通过RES诱导HER 3表达赋予乳腺癌细胞对紫杉醇细胞毒性的抗性。此外，观察到SIRT 1-FOXO 1信号通路在介导RES诱导的HER 3表达上调中起重要作用。综上所述，本研究揭示了RES诱导某些人乳腺癌细胞对紫杉醇耐药的机制，并提示RES和紫杉醇联合使用不适用于治疗表达HER 3蛋白的人乳腺癌。
Resveratrol (RES), a dietary phenolic compound, was reported to have cancer chemoprotective and chemotherapeutic effects. Earlier we unexpectedly observed that RES has a growth-enhancing effect in some breast cancer cells and can diminish the susceptibility of MDA-MB-231 and SKBR-3 cells to paclitaxel-induced cell death, but this phenomenon is not observed in MCF-7 cells. The present study seeks to determine the mechanism underlying RES's attenuation of paclitaxel cytotoxicity in cancer cells. It is found that RES reduces the anticancer action of paclitaxel only in the human breast cancer cells that express HER3 protein. Treatment of SKBR-3 cells with RES increases HER3 expression in a dose-dependent manner. The induction of HER3 expression by RES confers resistance of breast cancer cells against paclitaxel cytotoxicity. Furthermore, it is observed that the SIRT1-FOXO1 signaling pathway plays an important role in mediating RES-induced upregulation of HER3 expression. In conclusion, the present study reveals the mechanism for RES-induced resistance against paclitaxel in some human breast cancer cells, and it is suggested that the combined use of RES and paclitaxel is not suitable for treating human breast cancer that expresses HER3 protein.