Department of Oncology, Fujian Medical University Union Hospital, Fujian Medical University Fuzhou, Fujian, P.R. China.
Department of Respiratory Medicine, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian, P.R. China.
Curr Pharm Biotechnol. 2022;23(2):276-286. doi: 10.2174/1389201022666210217114825.
Dihydroartemisinin (DHA) exhibited anti-tumor effect in a variety of cancer cells, but its mechanism of action is unclear.
To investigate the therapeutic effects of DHA on Cisplatin (DDP)-resistant gastric cancer cell strain SGC7901/DDP and the possible molecular mechanism.
Cells were treated with DHA in a dose- and time-dependent manner, after which their proliferation, apoptosis, invasion, and migration abilities were evaluated. We further evaluated autophagy with mRFP-GFP-LC3 adenovirus transfection and transmission electron microscopy and also detected the expression levels of proteins (related to autophagy and apoptosis) via western blot. Meanwhile, the influence of DHA on cisplatin resistance was detected through a sensitization test and the evaluation of P-gp expression levels.
DHA effectively inhibited the proliferation, invasion, and migration of SGC7901/DDP cells and induced cell apoptosis which was accompanied by caspase-8/9/3 activation. Furthermore, exposure to DHA resulted in a pronounced increase in autophagy proteins, including Beclin-1 and LC3 II with PI3K/AKT/mTOR pathway inhibition. Additionally, enhancement of cisplatin sensitivity occurred in SGC7901/DDP cells treated with DHA, which was accompanied by P-gp downregulation.
DHA exerts an anti-cancer effect on SGC7901/DDP cells and the mechanisms possibly include enhancement of autophagy via PI3K/AKT/mTOR inhibition, inducement of apoptosis through caspase-dependent and mitochondrial pathway, and enhancement of cisplatin sensitivity through P-gp inhibition.
二氢青蒿素（DHA）在多种癌细胞中表现出抗肿瘤作用，但作用机制尚不清楚。
研究二氢青蒿素（DHA）对顺铂（DDP）耐药胃癌细胞株 SGC7901/DDP 的治疗作用及其可能的分子机制。
采用 DHA 剂量和时间依赖性处理细胞，评估其增殖、凋亡、侵袭和迁移能力。进一步通过 mRFP-GFP-LC3 腺病毒转染和透射电镜评估自噬，并通过 Western blot 检测相关蛋白（自噬和凋亡）的表达水平。同时，通过增敏试验和 P-gp 表达水平评估 DHA 对顺铂耐药性的影响。
DHA 有效抑制 SGC7901/DDP 细胞的增殖、侵袭和迁移，并诱导细胞凋亡，同时伴随着 caspase-8/9/3 的激活。此外，DHA 处理导致自噬蛋白（包括 Beclin-1 和 LC3 II）显著增加，PI3K/AKT/mTOR 通路被抑制。此外，DHA 处理 SGC7901/DDP 细胞可增强顺铂的敏感性，同时伴随着 P-gp 的下调。
DHA 对 SGC7901/DDP 细胞具有抗癌作用，其机制可能包括通过抑制 PI3K/AKT/mTOR 增强自噬、通过 caspase 依赖性和线粒体途径诱导凋亡以及通过抑制 P-gp 增强顺铂敏感性。
