Background/Objectives: Malignant pleural effusion (MPE) in lung cancer indicates systemically disseminated advanced lung cancer and is associated with poor survival. Intrapleural hyperthermic chemotherapy (IPHC) is a promising treatment for MPE; however, its biological basis is not fully understood. IPHC can enhance anticancer drug efficacy, particularly in drug-resistant cancers. This study investigated the effects of hyperthermia on cisplatin cytotoxicity in lung cancer cell lines, patient-derived tumor cells, and a patient-derived xenograft (PDX) model.Methods: Lung cancer cell lines (A549 and H2170) and patient-derived tumor cells were cultured in 2D/3D systems and treated with cisplatin under varying temperatures (37 °C, 43 °C, and 45 °C) and exposure times (5, 15, and 30 min). Antiproliferative effects were evaluated using LDH and CCK-8 assays. Optimal conditions identified in cell culture experiments were validated using a PDX model; tumor growth inhibition, delay, and protein expression were analyzed post-treatment.Results: Hyperthermia significantly enhanced the antitumor efficacy of cisplatin at 43 °C and 45 °C, with comparable effects under 15 and 30 min exposure. In the PDX model, IPHC showed increased tumor inhibition and necrosis and delayed tumor regrowth, particularly at higher cisplatin doses. Protein expression analysis revealed that hyperthermia decreased EGFR expression and increased levels of apoptosis-related proteins, including cleaved PARP and caspase-3.Conclusions: IPHC with cisplatin demonstrated enhanced antitumor efficacy in vitro models, particularly in drug-resistant lung cancer, indicating its potential as a valuable adjunct to existing treatment regimens for lung cancer and for improving patient outcomes in advanced lung cancer with MPE or pleural metastasis.
背景/目的：肺癌恶性胸腔积液（MPE）提示肺癌已发生系统性播散的晚期阶段，与不良预后相关。胸腔内热灌注化疗（IPHC）是治疗MPE的一种前景广阔的方法，但其生物学基础尚未完全阐明。IPHC可增强抗癌药物疗效，尤其对耐药性癌症具有显著作用。本研究探讨了热疗对肺癌细胞系、患者来源肿瘤细胞及患者来源异种移植（PDX）模型中顺铂细胞毒性的影响。 方法：在二维/三维培养体系中培养肺癌细胞系（A549和H2170）及患者来源肿瘤细胞，在不同温度（37°C、43°C和45°C）及暴露时间（5、15和30分钟）条件下给予顺铂处理。采用LDH和CCK-8法评估抗增殖效应。将细胞实验确定的最佳条件在PDX模型中进行验证，分析治疗后肿瘤生长抑制、延迟及蛋白表达变化。 结果：43°C和45°C热疗显著增强顺铂抗肿瘤疗效，15分钟与30分钟暴露时间效果相当。在PDX模型中，IPHC显示更强的肿瘤抑制和坏死效应，并延缓肿瘤再生，高剂量顺铂时尤为明显。蛋白表达分析表明热疗降低EGFR表达，同时上调凋亡相关蛋白（包括cleaved PARP和caspase-3）水平。 结论：顺铂联合IPHC在体外模型中显示出增强的抗肿瘤疗效，尤其对耐药性肺癌作用显著，提示其可作为现有肺癌治疗方案的重要辅助手段，有望改善伴有MPE或胸膜转移的晚期肺癌患者的临床结局。
Enhancing Intrapleural Hyperthermic Chemotherapy for Lung Cancer: Insights from 3D and PDX Models
肿瘤(癌症)患者之家