白藜芦醇是一种天然化合物，可能是改善传统乳腺癌治疗的替代方案。因此，我们评估了低剂量白藜芦醇在雌激素受体 (ER) 和人表皮生长因子受体 2 型 (HER2) 阳性乳腺癌细胞中增强常规疗法体外效果的能力。 乳腺癌细胞的细胞活力采用中性红摄取测定法进行测量。分别通过低渗荧光溶液测定、酸性囊泡细胞器的形成、流式细胞术和溴脱氧尿苷测定来检测细胞凋亡、自噬、细胞周期进展和细胞增殖。采用蛋白质印迹法研究促凋亡、抗凋亡和自噬蛋白以及雌激素受体的表达。白藜芦醇联合他莫昔芬代谢物或曲妥珠单抗分别降低 ER 和 HER2 阳性乳腺癌细胞的细胞活力。这种效应主要与由于亚二倍体细胞核形成增多、procaspase-7、Bcl-2、Bcl-xL 和 PARP 蛋白表达减少而诱导细胞凋亡有关。并增加了裂解的 PARP 的表达。白藜芦醇降低 ERα 的表达并增加 ERβ 的表达，导致乳腺癌细胞的活力降低。联合治疗诱导自噬，酸性囊泡细胞器水平增加和 p62/SQSTM1 蛋白降解证明了这一点。然而，用3-甲基腺嘌呤抑制自噬后，细胞活力进一步降低并诱导细胞凋亡，表明自噬具有促生存作用，损害细胞凋亡。白藜芦醇增加了乳腺癌细胞中常规疗法的体外细胞毒作用。然而，有必要阻止白藜芦醇诱导的自噬以改善治疗反应。© 2024。作者，获得日本乳腺癌协会的独家许可。

Resveratrol, a natural compound, may be an alternative to improving conventional breast cancer therapy. Thus, we assessed the capability of resveratrol at a low dose to enhance the in vitro effect of conventional theray in estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2)-positive breast cancer cells.Cell viability of breast cancer cells was measured with neutral red uptake assay. Apoptosis, autophagy, cell cycle progression and cell proliferation were detected through hypotonic fluorescent solution assay, formation of acidic vesicular organelles, flow cytometry, and bromodeoxyuridine assay, respectively. Western blotting was performed to study the expression of pro-apoptotic, anti-apoptotic and autophagic proteins, and estrogen receptors.Resveratrol combined with tamoxifen metabolites or trastuzumab reduced cell viability of ER- and HER2-positive breast cancer cells, respectively. This effect was mainly associated with induction of apoptosis due to a greater formation of hypodiploid nuclei, reduced protein expression of procaspase-7, Bcl-2, Bcl-xL, and PARP; and increased expression of cleaved PARP. Resveratrol decreased the expression of ERα and increased that of ERβ, contributing to the reduced viability on breast cancer cells. Combined treatments induced autophagy, evidenced by increased levels of acidic vesicular organelles and degradation of p62/SQSTM1 protein. Nevertheless, on inhibiting autophagy with 3-methyladenine, cell viability was further reduced and apoptosis was induced, suggesting a pro-survival role of autophagy, impairing apoptosis.Resveratrol increasead the in vitro cytotoxic effect of conventional therapy in breast cancer cells. However, it was necessary to block resveratrol-induced autophagy to improve the therapeutic response.© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.