Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
School of Medicine, Ningbo University, Ningbo 315020, P.R. China.
Biosci Rep. 2021 Jun 25;41(6). doi: 10.1042/BSR20210093.
Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25-30% of which have dysregulation in the PI3K/AKT pathway. The present study investigated the anticancer effect of erianin on TNBC cell line and its underlying mechanism.
After treatment with erianin, MTT assay was employed to determine the MDA-MB-231 and EFM-192A cell proliferation, the nucleus morphological changes were observed by DAPI staining. The cell cycle and apoptotic proportion were detected by flow cytometry. Western blot was performed to determine the cell cycle and apoptosis-related protein expression and PI3K pathways. Finally, the antiproliferative activity of erianin was further confirmed by adding or not adding PI3K agonists SC79.
Erianin inhibited the proliferation of MDA-MB-231 and EFM-192A cells in a dose-dependent manner, the IC50 were 70.96 and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G2/M phase, and the expressions of p21 and p27 were up-regulated, while the expressions of CDK1 and Cyclin B1 were down-regulated. Erianin also induced apoptosis via the mitochondrial pathway, with the up-regulation of the expression of Cyto C, PARP, Bax, active form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were down-regulated by erianin. After co-incubation with SC79, the cell inhibition rate of erianin was decreased, which further confirmed that the attenuated PI3K/Akt pathway was relevant to the pro-apoptotic effect of erianin.
Erianin can inhibit the proliferation of TNBC cells and induce cell cycle arrest and apoptosis, which may ascribe to the abolish the activation of the PI3K/Akt pathway.
三阴性乳腺癌（TNBC）是一种难治性乳腺癌亚型，其中 25-30%存在 PI3K/AKT 通路失调。本研究探讨了橙皮素对 TNBC 细胞系的抗癌作用及其潜在机制。
橙皮素处理后，采用 MTT 法检测 MDA-MB-231 和 EFM-192A 细胞增殖，DAPI 染色观察细胞核形态变化。流式细胞术检测细胞周期和凋亡比例。Western blot 检测细胞周期和凋亡相关蛋白表达及 PI3K 通路。最后，通过添加或不添加 PI3K 激动剂 SC79 进一步证实橙皮素的增殖抑制活性。
橙皮素呈剂量依赖性抑制 MDA-MB-231 和 EFM-192A 细胞增殖，IC50 分别为 70.96 和 78.58 nM。橙皮素可使细胞周期阻滞在 G2/M 期，上调 p21 和 p27 的表达，下调 CDK1 和 Cyclin B1 的表达。橙皮素还通过线粒体途径诱导细胞凋亡，上调 Cyto C、PARP、Bax、活性 Caspase-3 和 Caspase-9 的表达。此外，橙皮素下调 p-PI3K 和 p-Akt 的表达。与 SC79 共孵育后，橙皮素的细胞抑制率降低，进一步证实减弱的 PI3K/Akt 通路与橙皮素的促凋亡作用有关。
橙皮素可抑制 TNBC 细胞的增殖，诱导细胞周期阻滞和凋亡，可能归因于 PI3K/Akt 通路的失活。
