Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen 518172, China.
Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen 518172, China; Shenzhen Bay Laboratory, Shenzhen 518055, China.
Cancer Treat Res Commun. 2021;28:100386. doi: 10.1016/j.ctarc.2021.100386. Epub 2021 May 12.
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.
白藜芦醇（RES）是一种膳食酚类化合物，据报道具有抗癌化学预防和化疗作用。早些时候，我们意外地观察到 RES 对一些乳腺癌细胞具有促进生长的作用，并能降低 MDA-MB-231 和 SKBR-3 细胞对紫杉醇诱导的细胞死亡的敏感性，但这种现象在 MCF-7 细胞中观察不到。本研究旨在确定 RES 减弱癌细胞中紫杉醇细胞毒性的机制。结果发现，RES 仅在表达 HER3 蛋白的人乳腺癌细胞中降低了紫杉醇的抗癌作用。RES 处理 SKBR-3 细胞可剂量依赖性地增加 HER3 表达。RES 诱导的 HER3 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 SIRT1-FOXO1 信号通路在介导 RES 诱导的 HER3 表达上调中起重要作用。总之，本研究揭示了 RES 诱导的一些人乳腺癌细胞对紫杉醇耐药的机制，并表明 RES 和紫杉醇联合使用不适合治疗表达 HER3 蛋白的人乳腺癌。
