Artemisia gmelinii (Artemisia iwayomogi) has been used in traditional medicine to cure various infectious diseases such as cholecystitis, hepatitis, and jaundice. In this study, the Artemisiae Iwayomogii Herba ethanol extract was investigated for the ability to inhibit growth of hepatocellular carcinoma and its underlying mechanism involved. The antiproliferative effect of Artemisiae Iwayomogii Herba ethanol extract was evaluated using cell viability and proliferation assays. The effect of Artemisiae Iwayomogii Herba ethanol extract on apoptosis was measured using western blotting, terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling staining, JC-1 staining, cytochrome c release, immunohistochemistry, and immunofluorescence in ex vivo mouse xenografts. Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell growth and proliferation in a dose-dependent manner. The apoptotic effect of Artemisiae Iwayomogii Herba ethanol extract was observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling-positive apoptotic cells. Artemisiae Iwayomogii Herba ethanol extract also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell invasion and migration. In the ex vivo model, Artemisiae Iwayomogii Herba ethanol extract significantly inhibited tumor cell proliferation and increased the number of apoptotic cells with more activated cleaved caspase-3. A mechanistic study revealed that Artemisiae Iwayomogii Herba ethanol extract effectively suppressed the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma cells. Our findings demonstrate that Artemisiae Iwayomogii Herba ethanol extract can efficiently induce apoptosis and inhibit the growth, migration, and invasion of human hepatocellular carcinoma cells, and simultaneously block PI3K/AKT/mTOR pathway. We therefore suggest Artemisiae Iwayomogii Herba ethanol extract as a novel natural agent for prevention and therapy of hepatocellular carcinoma.

中文翻译：

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Artemisiae Iwayomogii Herba 抑制肝细胞癌细胞的生长、运动和 PI3K/AKT/mTOR 信号通路

青蒿（Artemisia iwayomogi）在传统医学中被用于治疗胆囊炎、肝炎、黄疸等多种传染病。在这项研究中，研究了艾蒿乙醇提取物抑制肝细胞癌生长的能力及其所涉及的潜在机制。使用细胞活力和增殖测定评估艾蒿乙醇提取物的抗增殖作用。使用蛋白质印迹、末端脱氧核苷酸转移酶介导的 dUTP-生物素末端标记染色、JC-1 染色、细胞色素 c 释放、免疫组织化学和免疫荧光在离体小鼠异种移植物中测量艾蒿乙醇提取物对细胞凋亡的影响。Artemisiae Iwayomogii Herba 乙醇提取物以剂量依赖性方式抑制肝细胞癌细胞的生长和增殖。通过增加裂解的 caspase-3 和裂解的 PARP 水平，以及末端脱氧核苷酸转移酶介导的 dUTP-生物素末端标记阳性细胞凋亡细胞的数量增加，观察到艾蒿乙醇提取物的凋亡作用。Artemisiae Iwayomogii Herba 乙醇提取物还通过线粒体膜电位的丧失降低了 XIAP 和 Mcl-1 的表达。此外，艾蒿乙醇提取物可抑制肝细胞癌细胞的侵袭和迁移。在离体模型中，艾蒿乙醇提取物显着抑制了肿瘤细胞增殖，并增加了具有更多活化裂解 caspase-3 的凋亡细胞数量。一项机制研究表明，艾蒿乙醇提取物可有效抑制肝细胞癌细胞中的 PI3K/AKT/mTOR 信号通路。我们的研究结果表明，艾蒿乙醇提取物可有效诱导人肝癌细胞凋亡并抑制其生长、迁移和侵袭，同时阻断 PI3K/AKT/mTOR 通路。因此，我们建议将艾蒿乙醇提取物作为预防和治疗肝细胞癌的新型天然药物。我们的研究结果表明，艾蒿乙醇提取物可有效诱导人肝癌细胞凋亡并抑制其生长、迁移和侵袭，同时阻断 PI3K/AKT/mTOR 通路。因此，我们建议将艾蒿乙醇提取物作为预防和治疗肝细胞癌的新型天然药物。我们的研究结果表明，艾蒿乙醇提取物可有效诱导人肝癌细胞凋亡并抑制其生长、迁移和侵袭，同时阻断 PI3K/AKT/mTOR 通路。因此，我们建议将艾蒿乙醇提取物作为预防和治疗肝细胞癌的新型天然药物。