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黄芪甲苷通过触发细胞凋亡和自噬增强卵巢癌细胞对顺铂的敏感性。

Astragaloside II enhanced sensitivity of ovarian cancer cells to cisplatin via triggering apoptosis and autophagy.

机构信息

Ethics Committee Office, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Heilongjiang, Harbin, China.

Department of Intensive Care Unit, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.

出版信息

Cell Biol Int. 2023 Sep;47(9):1600-1613. doi: 10.1002/cbin.12055. Epub 2023 Jun 15.

Abstract

Cisplatin (DDP) based chemotherapy occurs a reduced therapeutic effect on the later treatment of ovarian cancer (OC) due to DDP resistance. Astragaloside II (ASII), a natural product extracted from Radix Astragali, has shown promising anticancer effects. However, the effects of ASII on OC have not been clarified. In this study, we found that ASII inhibited cell growth and promoted cell apoptosis of DDP-resistant OC cells in vitro and in vivo. Further study showed that ASII downregulated multidrug resistance-related protein MDR1 and cell cycle-related protein Cyclin D1 and PCNA, and also upregulated apoptosis-related protein leaved PRAP and cleaved caspase-3. In addition, ASII induced autophagy, characterized by upregulation of LC3II expression, downregulation of p62 expression, and elevation of LC3 punctuation, may be associated with inhibition of the AKT/mTOR signaling pathway. Moreover, the messenger RNA-sequencing was used to identify potential molecules regulated by ASII. In conclusion, these findings indicated that ASII increased sensitivity of DDP in the treatment of OC.

摘要

顺铂(DDP)为基础的化疗在卵巢癌(OC)的后期治疗中由于 DDP 耐药而降低了治疗效果。黄芪甲苷 II(ASII),一种从黄芪中提取的天然产物,已显示出有希望的抗癌作用。然而,ASII 对 OC 的作用尚未阐明。在这项研究中,我们发现 ASII 在体外和体内抑制 DDP 耐药 OC 细胞的生长并促进细胞凋亡。进一步的研究表明,ASII 下调多药耐药相关蛋白 MDR1 和细胞周期相关蛋白 Cyclin D1 和 PCNA,同时上调凋亡相关蛋白 cleaved caspase-3 和 leaved PRAP。此外,ASII 诱导自噬,其特征为 LC3II 表达上调、p62 表达下调和 LC3 点状结构增加,可能与抑制 AKT/mTOR 信号通路有关。此外,信使 RNA 测序用于鉴定由 ASII 调节的潜在分子。总之,这些发现表明 ASII 增加了 DDP 在 OC 治疗中的敏感性。

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