研究葡萄酒加工的川芎炮制对增强奥莫来替尼治疗裸鼠脑内表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）异种移植的疗效的影响。在hCMEC / D3与PC9 NSCLC细胞的共培养系统中，使用流式细胞仪研究了WCR水提取物（2mg/mL）与奥莫来替尼（10和20μmol/L）联合作用对PC9细胞凋亡的影响。检查WCR提取物（0.5，1和2mg/mL）对ABCB1-MDCK单层细胞中8μmol/L奥莫来替尼的跨膜转运作用。采用Western blotting检测与血脑屏障完整性相关的紧密连接蛋白的表达。建立承载NSCLC异种移植瘤的裸鼠脑模型，观察WCR（1mg/g）联合奥莫来替尼（10mg/kg）对肿瘤生长的抑制作用。与仅奥莫来替尼（20μmol/L）相比，WCR提取物（2mg/mL）与奥莫来替尼联合使用显着增加了PC9细胞的凋亡率21％（P <0.01）。WCR（0.5，1，2mg/mL）的联合治疗明显提高了ABCB1-MDCK单层细胞中奥莫来替尼的顶层 - 底层转运（P <0.05）并显着降低了ZO-1，claudin-5和P-糖蛋白的表达水平（P <0.05）。在承载肿瘤的小鼠中，与仅奥莫来替尼相比，WCR和奥莫来替尼的联合治疗产生了更强的肿瘤抑制作用，改善了体重减轻，并延长了裸鼠的生存时间（P <0.05）。病理检查显示联合治疗明显增加了肿瘤细胞的凋亡率并减轻了脑部神经损伤。免疫组化显示WCR治疗显着降低了小鼠大脑中ZO-1和claudin-5的表达。WCR与奥莫来替尼联合使用可能会通过下调ZO-1，claudin-5和P-糖蛋白的表达，促进奥莫来替尼的跨膜转运，从而显示出更强的抑制EGFR突变NSCLC异种移植瘤的疗效。

To investigate the effect of wine-processed Chuanxiong Rhizoma (WCR) for enhancing the efficacy of aumolertinib against xenografts of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) in the brain of nude mice.In a co-culture system of hCMEC/D3 and PC9 NSCLC cells, the effect of aqueous extract of WCR (2 mg/mL) combined with aumolertinib (10 and 20 μmol/L) on apoptosis of PC9 cells was investigated using flow cytometry. The effects of WCR extract (0.5, 1, and 2 mg/mL) on transmembrane transport of 8 μmol/L aumolertinib was examined in ABCB1-MDCK monolayer cells. Western blotting was used to detect the expressions of the tight junction proteins related with blood- brain barrier integrity. A nude mouse model bearing NSCLC xenograft in the brain was established to observe the inhibitory effect of WCR (1 mg/g) combined with aumolertinib (10 mg/kg) on tumor growth.Compared with aumolertinib (20 μmol/L) alone, WCR extract (2 mg/mL) combined with aumolertinib significantly increased the apoptosis rate of PC9 cells by 21% (P < 0.01). The combined treatment with WCR (0.5, 1, 2 mg/mL) obviously increased apical-basolateral transport of aumolertinib in ABCB1-MDCK monolayer cells (P < 0.05) and significantly lowered the expression levels of zonula occludens-1, claudin-5 and P-glycoprotein (P < 0.05). In the tumor-bearing mice, compared with aumolertinib alone, the combined treatment with WCR and aumolertinib produced stronger inhibitory effect on tumor growth, improved weight loss, and prolonged the survival time of the nude mice (P < 0.05). Pathological examination showed that the combined treatment obviously increased the apoptosis rate of the tumor cells and alleviated neural injuries in the brain. Immunohistochemistry revealed that WCR treatment significantly reduced the expressions of ZO-1 and claudin-5 in the brain of the mice.WCR combined with aumolertinib shows stronger inhibitory effects against tumor xenografts of EGFR-mutant NSCLC possibly due to the effect of WCR in facilitating the transmembrane transport of aumolertinib by downregulating ZO-1, claudin-5 and P-glycoprotein expression.