耐药是表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）靶向治疗非小细胞肺癌（NSCLC）失败的主要原因，急需寻求新型有效药物以降低乃至逆转耐药。研究表明，维生素D（Vitamin D）类药物（活性vitamin D及其类似物）可抑制肿瘤细胞增殖、迁移及侵袭并可逆转化疗耐药，然而其对EGFR-TKI耐药的调控尚不明确。前期研究发现，在细胞和动物模型中，vitamin D类药物可与吉非替尼协同增效而降低耐药性；Vitamin D类药物抑制吉非替尼耐药细胞中claudin1、β-catenin、上皮间质转化及癌细胞干性相关标志物的表达。由此提出科学假说：Vitamin D类药物通过调控上述关键点抑制吉非替尼耐药。本项目拟采用吉非替尼耐药细胞的体外及体内模型，进一步研究vitamin D类药物抑制NSCLC吉非替尼耐药的作用及机制，为逆转NSCLC EGFR-TKI耐药提供新思路和新靶点。

Drug resistance is the main reason for the failure of targeted therapy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC), and there is an urgent need to explore new and effective drugs to reduce or even reverse drug resistance. Studies have shown that vitamin D (active vitamin D and its analogues) could inhibit tumor cell proliferation, migration and invasion, and could reverse chemotherapy resistance. However, whether vitamin D could regulate EGFR-TKI resistance is yet unclear. Our previous research found that vitamin D synergized with gefitinib to reduce gefitinib resistance both in cell and animal models; Vitamin D inhibited the expression of claudin1, β-catenin, epithelial mesenchymal transition and cancer cell stemness - related markers in gefitinib-resistant cells. Therefore, we speculate that vitamin D inhibit gefitinib resistance by regulating the above key points. This research intends to further study the role and mechanism of vitamin D inhibiting gefitinib resistance in NSCLC by using in vitro and in vivo models of gefitinib-resistant cells. Our research provides new ideas and targets for reversing EGFR-TKI resistance in NSCLC.