Lung adenocarcinoma patients with epidermal growth factor receptor (EGFR)-activating mutations respond well to tyrosine kinase inhibitors but typically develop resistance. Current therapies mainly target differentiated cells, not cancer stem cells (CSCs), but CSCs affect the occurrence, invasion, metastasis and treatment sensitivity of malignant tumours. Recently, aerobic exercise has emerged as adjuvant therapy for cancer. Aerobic exercise can accelerate blood circulation, improve tissue oxygen supply, reduce the stress level of patients, improve the antioxidant capacity of the body, and facilitate the degradation of hypoxia-inducible factor-1 (HIF-1) in tumour tissues, thus weakening its maintenance effect on CSCs. In this study, we successfully established lung adenocarcinoma cell lines with gefitinib resistance. Long-term gefitinib induction could increase the level of oxidative stress in lung adenocarcinoma cells and reduce the antioxidant capacity, resulting in the high expression of HIF-1 and ALDH1 and leading to the enrichment of CSCs, and a decreased response to gefitinib. This may be one of the important reasons for gefitinib-acquired resistance in lung adenocarcinoma. In the case of drug resistance, effective aerobic exercise could reduce ROS, activate SOD, inhibit HIF-1 and ALDH1, and cause a reduction in CSCs to sensitise cells to gefitinib again and ultimately inhibit the malignant proliferation of tumours. Therefore, in the treatment of lung adenocarcinoma, the inhibitory effect of aerobic exercise on oxidative stress can enhance the response of drug-resistant cells to gefitinib and can be used as an effective adjunct measure in the treatment of lung adenocarcinoma.

具有表皮生长因子受体 (EGFR) 激活突变的肺腺癌患者对酪氨酸激酶抑制剂反应良好，但通常会产生耐药性。目前的治疗主要针对分化细胞，而不是癌症干细胞（CSCs），但CSCs影响恶性肿瘤的发生、侵袭、转移和治疗敏感性。最近，有氧运动已成为癌症的辅助疗法。有氧运动可以加速血液循环，改善组织供氧，减轻患者的压力水平，提高机体的抗氧化能力，促进肿瘤组织中缺氧诱导因子-1（HIF-1）的降解，从而削弱其对 CSC 的维持作用。在本研究中，我们成功建立了吉非替尼耐药的肺腺癌细胞系。长期吉非替尼诱导可增加肺腺癌细胞氧化应激水平，降低抗氧化能力，导致HIF-1和ALDH1高表达，导致CSCs富集，对吉非替尼的反应降低。这可能是肺腺癌吉非替尼获得性耐药的重要原因之一。在耐药的情况下，有效的有氧运动可以减少ROS，激活SOD，抑制HIF-1和ALDH1，导致CSC减少，使细胞再次对吉非替尼敏感，最终抑制肿瘤的恶性增殖。因此，在肺腺癌的治疗中，