穿心莲内酯 (Andro) 是穿心莲 (Andrographis fan) (Burm.f.) Wall 的提取物。 ex Nees（棘科），具有多种生物活性特性。然而，Andro对胰腺癌（PC）的确切机制和作用仍不清楚。通过体外实验和异种移植小鼠模型研究了Andro的细胞毒性潜力及其对PC细胞的潜在机制。 PC 细胞首先接受不同浓度的 Andro 处理。使用流式细胞术和 DCFH-DA 染色评估活性氧 (ROS)。流式细胞术检测细胞凋亡率。此外，应用蛋白质印迹法评估 cleaved-caspase-3、DJ-1、LC3-I、LC3-II 和 p62 的表达水平。为了进一步阐明 ROS 积累和自噬的参与，我们采用 N-乙酰半胱氨酸作为 ROS 的清除剂，并使用 3-甲基腺嘌呤作为自噬的抑制剂。Andro 在体外和实验中均表现出对 PC 细胞的有效抗增殖作用并诱导细胞凋亡。体内。 Andro 对 PC 细胞的细胞毒性被 DJ-1 过表达所抵消。 Andro引起的DJ-1表达减少导致ROS积累，随后抑制PC细胞的生长。此外，Andro 刺激细胞保护性自噬，从而削弱抗肿瘤作用。自噬的药理学阻断进一步增强了Andro的抗肿瘤功效。我们的研究表明，DJ-1减少诱导的ROS积累在Andro介导的PC细胞抑制中发挥了关键作用。此外，Andro 在 PC 细胞中诱导的保护性自噬是未来研究中需要解决的机制。©2024 Wang 等人。

Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear.The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy.Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo. The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro.Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.©2024 Wang et al.