Department of General Surgery, The First Affiliated Hospital, Jiamusi University, 154003, Jiamusi, Heilongjiang Province, China.
Department of Medical Oncology, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China.
Mol Biol Rep. 2022 Jul;49(7):5897-5909. doi: 10.1007/s11033-022-07371-8. Epub 2022 May 11.
Coix seed oil (CSO) has a wide range of anticancer effects. However, the mechanism of action against pancreatic cancer (PC) and regulation of mitochondria in vitro is still unclear.
This research investigated the possible mechanism of CSO induction of PC cell apoptosis and regulating mitochondrial functional damage. Proliferation of PC cells, mitochondrial membrane potential (MMP), qualitative and quantitative analysis of PC cell apoptosis, openness of mitochondrial permeability transition pore, related protein expression, generation of reactive oxygen species (ROS), and gene expression were determined by cell counting kit-8, JC-1 staining, acridine orange and ethidium bromide staining, flow cytometry, calcein-AM/cobalt staining, western blotting, dichlorofluorescein diacetate probe, and quantitative real-time reverse transcription-polymerase chain reaction, respectively. We confirmed that PTEN protein was involved in CSO-induced PANC-1 cell apoptosis and mitochondrial functional damage. CSO induced depolarization of MMP, increased opening of the mitochondrial permeability transition pore, increased ROS production, and further increased mitochondrial damage. Additionally, CSO downregulated expression of p-AKT and p-PI3K proteins; upregulated protein expression of cleaved caspase-9, Bax, cleaved caspase-3 and cytochrome c; and downregulated expression of Bcl-2 by upregulating the PTEN gene. The corresponding protein expression was consistent with the gene expression level. Furthermore, the loss of function of PTEN protein reduces the ability of CSO to induce apoptosis of PANC-1 cells and damage to mitochondrial function.
CSO induces apoptosis of PANC-1 PC cells by modulating mitochondrial functional impairment and related apoptotic molecules via PTEN, which may be closely related to the PI3K/AKT signaling pathway.
薏苡仁油（CSO）具有广泛的抗癌作用。然而，其体外抗胰腺癌（PC）作用机制及调控线粒体的作用机制尚不清楚。
本研究旨在探讨 CSO 诱导 PC 细胞凋亡及调控线粒体功能损伤的可能机制。采用细胞计数试剂盒-8（CCK-8）法、JC-1 染色法、吖啶橙/溴化乙锭（AO/EB）染色法、流式细胞术、钙黄绿素 AM/钴染色法、Western blot 法、二氯荧光素二乙酸探针（DCFH-DA）法和实时荧光定量聚合酶链式反应（qRT-PCR）分别检测 CSO 对 PC 细胞增殖、线粒体膜电位（MMP）、PC 细胞凋亡的定性和定量分析、线粒体通透性转换孔（mPTP）的开放程度、相关蛋白表达、活性氧（ROS）的产生以及基因表达的影响。我们证实，PTEN 蛋白参与 CSO 诱导的 PANC-1 细胞凋亡和线粒体功能损伤。CSO 诱导 MMP 去极化，增加 mPTP 开放，增加 ROS 产生，进一步加重线粒体损伤。此外，CSO 通过上调 PTEN 基因下调 p-AKT 和 p-PI3K 蛋白表达，上调 cleaved caspase-9、Bax、cleaved caspase-3 和细胞色素 c 蛋白表达，下调 Bcl-2 蛋白表达。相应的蛋白表达与基因表达水平一致。此外，PTEN 蛋白功能丧失降低了 CSO 诱导 PANC-1 细胞凋亡和损伤线粒体功能的能力。
CSO 通过调节线粒体功能障碍和相关凋亡分子诱导 PANC-1 PC 细胞凋亡，这可能与 PI3K/AKT 信号通路密切相关。
