Department of Anesthesiology, Yantaishan Hospital, 264000 Yantai, Shandong, China.
Laboratory Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), 266000 Qingdao, Shandong, China.
Discov Med. 2024 Nov;36(190):2231-2243. doi: 10.24976/Discov.Med.202436190.205.
Lung cancer treatment remains a global challenge due to tumor cell resistance. Propofol, traditionally used as an anesthetic, has demonstrated potential anti-tumor properties. This study seeks to elucidate how propofol induces cell death in lung cancer cells by upregulating Pannexin 1 (PANX1) expression, activating the mitochondrial cell death pathway, and augmenting reactive oxygen species (ROS) production.
In this study, the A549 lung cancer cell line was employed as the experimental model. Cells underwent exposure to varying propofol concentrations and were pre-treated with HO and N-acetylcysteine (NAC) to simulate oxidative stress and antioxidant conditions. Various techniques, including 5-Ethynyl-2'-deoxyuridine (EdU), colony formation, Transwell, 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL), and JC-1 (5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide) probes, were employed to evaluate propofol's effects on lung cancer cell viability, growth, invasion, ROS levels, apoptosis, and mitochondrial membrane potential. Western blot analysis was used to measure PANX1, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, and Cytochrome C (Cyt C) protein levels. Additionally, PANX1's influence on propofol-induced apoptosis was investigated through siRNA interference.
The experiment unveiled propofol's dose-dependent inhibition of A549 lung cancer cell growth, coupled with decreased cell proliferation and invasion attributable to heightened ROS production. Notably, propofol treatment significantly elevated mitochondrial membrane potential, signifying activation of the mitochondrial cell death pathway ( < 0.01). Furthermore, propofol upregulated PANX1 expression ( < 0.01), thereby intensifying apoptosis signaling, whereas PANX1 inhibition ameliorated propofol-induced apoptosis ( < 0.01). These findings underscore the pivotal role of PANX1 upregulation and ROS augmentation in propofol-induced apoptosis in lung cancer cells.
This study provides evidence that propofol induces cell death in lung cancer cells by upregulating PANX1, activating the mitochondrial apoptosis pathway, and increasing ROS production. These findings suggest that targeting PANX1 and ROS could enhance the anti-cancer efficacy of propofol in lung cancer.
由于肿瘤细胞耐药性，肺癌的治疗仍然是一个全球性的挑战。丙泊酚传统上被用作麻醉剂，已显示出具有潜在的抗肿瘤特性。本研究旨在阐明丙泊酚如何通过上调 Pannexin 1（PANX1）表达、激活线粒体细胞死亡途径以及增加活性氧（ROS）产生来诱导肺癌细胞死亡。
本研究采用 A549 肺癌细胞系作为实验模型。细胞接受不同浓度的丙泊酚处理，并预先用 HO 和 N-乙酰半胱氨酸（NAC）处理，以模拟氧化应激和抗氧化条件。采用 5-乙炔基-2'-脱氧尿苷（EdU）、集落形成、Transwell、2'，7'-二氯二氢荧光素二乙酸酯（DCFH-DA）、末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）和 JC-1（5,5',6,6'-四氯-1,1',3,3'-四乙基-碘化咪唑羰花青）探针等多种技术评估丙泊酚对肺癌细胞活力、生长、侵袭、ROS 水平、细胞凋亡和线粒体膜电位的影响。Western blot 分析用于测量 PANX1、B 细胞淋巴瘤 2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）、半胱天冬酶 3 和细胞色素 C（Cyt C）蛋白水平。此外，通过 siRNA 干扰研究了 PANX1 对丙泊酚诱导的细胞凋亡的影响。
实验揭示了丙泊酚对 A549 肺癌细胞生长的剂量依赖性抑制作用，同时由于 ROS 产生增加，细胞增殖和侵袭能力下降。值得注意的是，丙泊酚处理显著增加线粒体膜电位，表明线粒体细胞死亡途径的激活（<0.01）。此外，丙泊酚上调 PANX1 表达（<0.01），从而增强凋亡信号，而 PANX1 抑制可改善丙泊酚诱导的细胞凋亡（<0.01）。这些发现强调了 PANX1 上调和 ROS 增加在丙泊酚诱导肺癌细胞凋亡中的关键作用。
本研究表明，丙泊酚通过上调 PANX1、激活线粒体凋亡途径和增加 ROS 产生来诱导肺癌细胞死亡。这些发现表明，靶向 PANX1 和 ROS 可能增强丙泊酚在肺癌中的抗癌疗效。
