This study investigated the effect of ellagic acid (EA) on SKOV‐3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin‐like growth factor‐1 (IGF‐1), a PI3K/Akt activator. EA, at an IC₅₀ of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV‐3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin‐1, ATG‐5, LC3I/II, Bax, cleaved caspase‐3/8 and reduced those of p62 and Bcl‐2 in these cancer cells. Mechanistically, EA decreased levels of p‐S6K1 (Thr³⁸⁹) and 4EBP‐1 (Thr^37/46), two downstream targets of mTORC1, and p‐Akt (Thr³⁰⁸) but increased levels of AMPK (Thr¹⁷²) and p‐raptor (Ser⁷⁹²), a natural inhibitor of mTORC1. CC or IGF‐1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin‐1, and cleaved caspase‐3. In conclusion, EA can inhibit SKOV‐3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.

中文翻译：

---

鞣花酸在 SKOV-3 卵巢癌细胞中的抗肿瘤作用需要通过抑制 Akt 和激活 AMPK 来激活自噬。

本研究调查了鞣花酸 (EA) 对 SKOV-3 细胞生长和侵袭性的影响，并测试了其潜在机制是否涉及调节自噬。在存在或不存在氯喹 (CQ)、自噬抑制剂、化合物 C (CC)、AMPK 抑制剂或胰岛素样生长因子-1 (IGF-1)、PI3K/Akt 激活剂的情况下，用 EA 处理细胞. EA 的 IC ₅₀为 36.6 µmol/L，可抑制 SKOV-3 细胞的细胞增殖、迁移和侵袭并诱导细胞凋亡。这些事件被 CQ 阻止了。此外，EA 增加了 Beclin-1、ATG-5、LC3I/II、Bax、裂解的 caspase-3/8 的水平，并降低了这些癌细胞中 p62 和 Bcl-2 的水平。从机制上讲，EA 降低了 p-S6K1 (Thr ³⁸⁹ ) 和 4EBP-1 (Thr ^37/46)，mTORC1 的两个下游靶标和 p-Akt (Thr ³⁰⁸ )，但增加了 AMPK (Thr ¹⁷² ) 和 p-raptor (Ser ⁷⁹² )（mTORC1 的天然抑制剂）的水平。单独使用 CC 或 IGF-1 部分阻止了 EA 对细胞存活、细胞侵袭以及 LDH、Beclin-1 和裂解的 caspase-3 水平的影响。总之，EA可以通过激活由mTORC1和Akt的抑制以及AMPK的激活介导的细胞毒性自噬来抑制SKOV-3的生长、迁移和侵袭。