摘 要：肿瘤异质性、耐药性及系统性毒副作用严重制约了现有癌症治疗策略的临床疗效，亟需开发更为安全且精准的干预手段。我们之前的研究表明，血管增生靶向交变电场（ATEF）作为一种非侵入性物理治疗方法，可以显著抑制胶质母细胞的生长。在此基础上，本研究评估了ATEF在非小细胞肺癌（NSCLC）模型中的抗肿瘤作用，并系统探讨其潜在的分子机制。通过在C57BL/6小鼠（Mus musculus）中建立Lewis肺癌皮下移植瘤模型，研究发现ATEF在不引起明显体重变化的前提下显著抑制了肿瘤生长。转录组学分析显示，ATEF显著下调铁死亡关键调控因子Slc7a11，并上调脂质代谢受体基因Vldlr。代谢组学结果进一步表明，ATEF诱导肿瘤组织脂质与能量代谢发生显著重塑，多种磷脂类代谢物及花生四烯酸代谢通路上调。联合转录组与代谢组分析揭示，Slc7a11与膜脂代谢物呈负相关，Vldlr与花生四烯酸及磷脂代谢物呈正相关，提示ATEF可能通过协同调控氧化应激与脂质代谢网络，增强铁死亡敏感性，进而干扰血管生成来抑制肿瘤生长。综上，本研究揭示了ATEF通过物理电场诱导肿瘤微环境内基因转录和代谢重编程，从而抑制NSCLC生长的机制，为进一步拓展ATEF的临床应用奠定了重要基础。
关键词：血管增生靶向交变电场；非小细胞肺癌；肿瘤电场治疗；肿瘤微环境；铁死亡
中图分类号：R730.5；R454                      文献标志码：A               DOI：10.3969/j.issn.1007-7146.2026.03.006

Abstract: Tumor heterogeneity, drug resistance, and systemic toxicities severely limit the clinical efficacy of current cancer therapies, highlighting the urgent need for safer and more precise therapeutic strategies. Our previous work demonstrated that angiogenesis-targeted electric fields (ATEF), a non-invasive biophysical treatment modality, can significantly inhibit the growth of glioblastoma. Based on these findings, the present study evaluated the antitumor effects of ATEF in a non-small cell lung cancer (NSCLC) model and systematically investigated its underlying molecular mechanisms. Using a subcutaneous Lewis lung carcinoma xenograft model in C57BL/6 mice (Mus musculus) , we found that ATEF treatment markedly suppressed tumor growth without inducing significant body weight changes. Transcriptomic profiling revealed that ATEF significantly downregulated Slc7a11, a key regulator of ferroptosis, while upregulating Vldlr, a gene encoding a lipid metabolism receptor. Metabolomic analysis further demonstrated that ATEF induced pronounced remodeling of lipid and energy metabolism in tumor tissues, with multiple phospholipid species and arachidonic acid metabolic pathways being upregulated. Integrated transcriptomic and metabolomic analyses revealed that Slc7a11 was negatively correlated with membrane lipid metabolites, whereas Vldlr was positively correlated with arachidonic acid and phospholipid metabolites, suggesting that ATEF may enhance ferroptosis sensitivity by coordinately regulating oxidative stress and lipid metabolic networks, thereby interfering with angiogenesis and ultimately suppressing tumor growth. Collectively, our findings reveal that ATEF suppresses NSCLC growth by inducing transcriptional and metabolic reprogramming within the tumor microenvironment through biophysical electric field modulation, providing a mechanistic basis for further clinical translation of this novel therapeutic approach.
Keywords: angiogenesis-targeted electric fields; non-small cell lung cancer; tumor treating fields; tumor microenvironment; ferroptosis
（Acta Laser Biology Sinica, 2026, 35(3): 241-252）