耐药性是肿瘤化疗失败的关键因素。它增强癌细胞的干细胞样特性、肿瘤转移和复发。木犀草素是一种天然黄酮类化合物，具有很强的抗肿瘤作用。然而，木犀草素预防紫杉醇 (PTX) 耐药癌细胞的机制仍有待阐明。采用细胞计数试剂盒8法检测木犀草素对EC1/PTX和EC1细胞增殖的抑制作用。使用集落形成和流式细胞术测定来评估集落形成能力、细胞周期和细胞凋亡。采用伤口愈合和Transwell侵袭实验研究木犀草素对EC1/PTX细胞迁移和侵袭的影响。 Western blotting用于检测球体形成后EMT相关蛋白和干细胞标记物的蛋白水平。通过高通量测序筛选亲本细胞和耐药细胞，检测RNA和差异基因的差异表达。采用ELISA和Western blotting对筛选的PI3K/Akt信号通路进行验证，并通过分子对接探索其关键蛋白。采用苏木精-伊红染色和TUNEL染色观察裸鼠移植瘤的形态和凋亡情况。本研究发现，木犀草素在体外抑制 PTX 耐药食管鳞状细胞癌 (ESCC) 细胞的肿瘤抵抗（抑制增殖、诱导细胞周期停滞和细胞凋亡、阻碍迁移侵袭、EMT 和干细胞球形化）。此外，木犀草素与PTX联合使用可增强药物敏感性并促进耐药ESCC细胞的凋亡。从机制上讲，木犀草素可能通过与粘着斑激酶 (FAK)、Src 和 AKT 的活性位点结合来抑制 PI3K/AKT 信号通路。值得注意的是，木犀草素降低了 PTX 耐药性 ESCC 细胞的致瘤潜力，但在体内并未表现出明显的毒性。木犀草素通过下调 PTX 耐药性 ESCC 中的 FAK/PI3K/AKT 通路来增强药物化疗敏感性，可能成为治疗 PTX 耐药性 ESCC 癌症的有前途的药物。

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem‑like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti‑tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)‑resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit‑8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT‑related proteins and stem cell markers after sphere formation. Parental cells and drug‑resistant cells were screened by high‑throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX‑resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug‑resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX‑resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX‑resistant ESCC and could be a promising agent for the treatment of PTX‑resistant ESCC cancers.