Department of Pharmacy, The 305 Hospital of PLA, Beijing, China.
Medical School of Chinese PLA, Beijing, China.
Braz J Med Biol Res. 2021 Oct 18;54(12):e11183. doi: 10.1590/1414-431X2021e11183. eCollection 2021.
Due to the high mortality and rapid disease progression, ovarian cancer remains one of the most common malignancies threatening the health of women. The present study was conducted to explore the anticancer effects and the underlying mechanisms of poricoic acid A (PAA), the main components of Poria cocos, on ovarian cancer. We investigated the anticancer effects of different concentrations of PAA in the SKOV3 cell line. Cell viability and proliferation were examined by CCK-8 assay. Cellular migration and invasion were assessed by the scratch and Transwell migration assays, respectively. The effect of PPA on cell apoptosis was measured by flow cytometry and caspase-3/8/9 colorimetric assay. Western blot was performed to detect protein level changes related to apoptosis and mTOR signaling pathways. The in vivo anticancer effect of PAA was evaluated using xenograft tumorigenesis model in nude mice. Our results showed that PAA suppressed SKOV3 cellular viability, migration, and invasion in a dosage-dependent manner. Flow cytometry results demonstrated PAA treatment could induce SKOV3 cell apoptosis. In addition, increased ratio of LC3-II/LC3-I (a marker for autophagosome formation) was observed after PAA treatment, as well as inhibition of m-TOR and p70s6k phosphorylation. In nude mice, PAA treatment reduced the xenograft tumor weight by 70% (P<0.05). In conclusion, our data suggested that PAA induced apoptosis and autophagy in ovarian cancer via modulating the mTOR/p70s6k signaling axis.
由于卵巢癌的死亡率高且疾病进展迅速，仍然是威胁女性健康的最常见恶性肿瘤之一。本研究旨在探讨多孔菌酸 A（PAA）（多孔菌的主要成分）对卵巢癌的抗癌作用及其潜在机制。我们研究了不同浓度的 PAA 在 SKOV3 细胞系中的抗癌作用。通过 CCK-8 测定法检测细胞活力和增殖。通过划痕和 Transwell 迁移测定法分别评估细胞迁移和侵袭。通过流式细胞术和 caspase-3/8/9 比色法测定 PPA 对细胞凋亡的影响。通过 Western blot 检测与细胞凋亡和 mTOR 信号通路相关的蛋白水平变化。使用裸鼠异种移植肿瘤模型评估 PAA 的体内抗癌作用。我们的结果表明，PAA 以剂量依赖性方式抑制 SKOV3 细胞活力、迁移和侵袭。流式细胞术结果表明 PAA 处理可诱导 SKOV3 细胞凋亡。此外，在 PAA 处理后观察到 LC3-II/LC3-I 的比值增加（自噬体形成的标志物），并且 m-TOR 和 p70s6k 磷酸化受到抑制。在裸鼠中，PAA 处理使异种移植肿瘤重量减少了 70%（P<0.05）。总之，我们的数据表明，PAA 通过调节 mTOR/p70s6k 信号轴诱导卵巢癌细胞凋亡和自噬。
