Huang Shaoyan, Li Quanxing, Song Yaobo
Department of Medical Oncology, Yantaishan Hospital Affiliated to Binzhou Medical University, 10087, Science and Technology Avenue, Laishan District, Yantai, 264003, Shandong, China.
Department of Cardiothoracic Surgery, Dongying People's Hospital, Dongying, 257000, Shandong, China.
Discov Oncol. 2024 Sep 30;15(1):510. doi: 10.1007/s12672-024-01361-x.
Non-small cell lung cancer (NSCLC) represents a prevalent and challenging malignancy, often posing difficulties in treatment due to late-stage diagnosis and limited therapeutic options.
This study aims to elucidate the impact of Codonopsis pilosula polysaccharide (CPP) on NSCLC, exploring its potential anticancer molecular mechanisms.
Purchase A549 cells and treat them with varying concentrations of CPP, dividing them into groups. Use CCK-8 assays for cell proliferation and TUNEL assays for apoptosis detection. Perform Western blot (WB) to detect NF-κB p65, pNF-κB p65, and pyroptosis-related proteins. Measure ROS, inflammatory factors, and LDH levels using kits. Observe pyroptosis morphology under a microscope. Inoculate A549 cells subcutaneously into nude mice to create a xenograft model and treat them with daily CPP injections. Collect tumor tissues, measure tumor volume and mass. Perform TUNEL immunohistochemistry for apoptosis and H&E staining for tumor histology. Detect pyroptosis-related proteins with Western blot and immunohistochemistry, and assess inflammatory factors using ELISA and immunohistochemistry.
The research reveals a concentration-dependent inhibitory effect of CPP on A549 cell viability, with optimal efficacy observed at 40 μmol/L CPP. CPP demonstrates the capacity to induce apoptosis, mediate NF-κB activation, and accumulate reactive oxygen species (ROS). Notably, CPP promotes pyroptosis in A549 cells and in vivo, upregulating pyroptosis-related proteins. In vivo administration of CPP significantly inhibits tumor growth, accompanied by notable morphological and histological alterations. Additionally, both in vitro and in vivo studies confirm elevated levels of IL-1β and IL-18 in tumor tissues following CPP treatment.
In conclusion, CPP, as a multifaceted agent, suppresses the progression of NSCLC by inducing NLRP3/GSDMD-dependent pyroptosis. This research provides valuable insights into the therapeutic potential of CPP and stimulates further exploration for its integration into future NSCLC treatments.
非小细胞肺癌（NSCLC）是一种常见且具有挑战性的恶性肿瘤，由于晚期诊断和有限的治疗选择，其治疗常常面临困难。
本研究旨在阐明党参多糖（CPP）对非小细胞肺癌的影响，探索其潜在的抗癌分子机制。
购买A549细胞，用不同浓度的CPP处理，将其分组。使用CCK-8法检测细胞增殖，TUNEL法检测细胞凋亡。进行蛋白质免疫印迹（WB）检测NF-κB p65、磷酸化NF-κB p65和焦亡相关蛋白。使用试剂盒测量活性氧（ROS）、炎症因子和乳酸脱氢酶（LDH）水平。在显微镜下观察焦亡形态。将A549细胞皮下接种到裸鼠体内建立异种移植模型，每天注射CPP进行治疗。收集肿瘤组织，测量肿瘤体积和质量。进行TUNEL免疫组织化学检测细胞凋亡，苏木精-伊红（H&E）染色观察肿瘤组织学。用蛋白质免疫印迹和免疫组织化学检测焦亡相关蛋白，用酶联免疫吸附测定（ELISA）和免疫组织化学评估炎症因子。
研究显示CPP对A549细胞活力具有浓度依赖性抑制作用，在40μmol/L CPP时观察到最佳效果。CPP具有诱导细胞凋亡、介导NF-κB激活和积累活性氧（ROS）的能力。值得注意的是，CPP在A549细胞和体内均促进焦亡，上调焦亡相关蛋白。CPP体内给药显著抑制肿瘤生长，并伴有明显的形态学和组织学改变。此外，体外和体内研究均证实CPP治疗后肿瘤组织中白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）水平升高。
总之，CPP作为一种多效性药物，通过诱导NLRP3/ Gasdermin D（GSDMD）依赖性焦亡抑制非小细胞肺癌的进展。本研究为CPP的治疗潜力提供了有价值的见解，并激发了对其纳入未来非小细胞肺癌治疗的进一步探索。
