Liu Xingchen, Zhang Xin, Mi Lida, Zhang Hailin, Shi Woda
Department of Cardiothoracic Surgery, Affiliated Hospital 6 of Nantong University, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, Yancheng, Jiangsu, 224000, China.
Department of Pneumology, Affiliated Hospital 6 of Nantong University, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, Yancheng, Jiangsu, 224000, China.
Curr Pharm Biotechnol. 2025;26(6):902-910. doi: 10.2174/0113892010303032240902063213.
To improve the prognosis outcome of lung cancer patients, more investigations are still needed. Previous reports have demonstrated the function of Ferulic Acid (FA) in lung cancer; thus, we have attempted to probe more molecular mechanisms underlying FA application in lung cancer.
CCK8 and colony formation experiments have been employed to explore cell viability and proliferation. Cell apoptosis was evaluated through flow cytometry. Cell morphology was observed with a microscope. MMP was assessed by JC-1 and LDH activity was evaluated by relative kit. Western blot assays were performed to examine the expression levels of GSDMD, GSDMD-N, caspase family proteins, and ROS/JNK/Bax mitochondrial apoptosis pathway downstream proteins. Flow cytometry analysis also measured the level of ROS. Tissues from animal models were taken for IHC analysis of C-caspase-1.
FA was found to inhibit proliferation, change cell morphology, decrease MMP, and enhance LDH activity, suggesting its ability to induce pyroptosis of lung cancer cells. Both caspase-1 and GSDMD were found to be involved in the pyroptosis of lung cancer cells treated with FA, and caspase-1 mediated GSDMD. Moreover, FA was validated to regulate pyroptosis by ROS/JNK/Bax mitochondrial apoptosis pathway and .
In summary, FA regulates GSDMD through ROS/JNK/Bax mitochondrial apoptosis pathway to induce pyroptosis in lung cancer cells, which may offer a theoretical basis for pyroptosis in the occurrence of lung cancer.
为改善肺癌患者的预后结果，仍需要更多研究。先前的报道已证实阿魏酸（FA）在肺癌中的作用；因此，我们试图探究FA应用于肺癌的更多分子机制。
采用CCK8和集落形成实验来探究细胞活力和增殖。通过流式细胞术评估细胞凋亡。用显微镜观察细胞形态。用JC-1评估线粒体膜电位（MMP），并用相关试剂盒评估乳酸脱氢酶（LDH）活性。进行蛋白质免疫印迹分析以检测gasdermin D（GSDMD）、GSDMD-N、半胱天冬酶家族蛋白以及活性氧/应激活化蛋白激酶/凋亡蛋白酶激活因子-1（ROS/JNK/Bax）线粒体凋亡途径下游蛋白 的表达水平。流式细胞术分析还测量了ROS水平。取动物模型的组织进行半胱天冬酶-1（C-caspase-1）的免疫组化分析。
发现FA可抑制增殖、改变细胞形态、降低MMP并增强LDH活性，表明其具有诱导肺癌细胞焦亡的能力。发现半胱天冬酶-1和GSDMD均参与了经FA处理的肺癌细胞的焦亡，且半胱天冬酶-1介导GSDMD。此外，证实FA通过ROS/JNK/Bax线粒体凋亡途径调节焦亡。
总之，FA通过ROS/JNK/Bax线粒体凋亡途径调节GSDMD以诱导肺癌细胞焦亡，这可能为肺癌发生中的焦亡提供理论依据。
