为了探究姜黄素在逆转非小细胞肺癌对抗癌药物吉非替尼耐药性中的作用机制,从而提高吉非替尼的治疗效果,以 A549 细胞系为实验细胞,成功建立了吉非替尼耐药的 A549（A549／GR）细胞系。将其分为 4 个治疗组:对照组、吉非替尼组、姜黄素组、吉非替尼联合姜黄素治疗组.分别使用细胞计数试剂盒-8（CCK-8）、集落形成、transwell和流式细胞术评估 A549 和 A549／GR 细胞的存活率、克隆形成能力、迁移、侵袭和凋亡。通过蛋白质印迹实验研究了与细胞凋亡、上皮间质转化（EMT）和 AKT 信号传导相关的蛋白质,通过 RT-PCR 实验检测了 A549 和 A549／GR 细胞中 MET 和 AXL 基因的表达水平差异。结果显示:①吉非替尼和姜黄素联合治疗具有协同作用,增强了化疗敏感性和细胞凋亡,同时抑制了细胞增殖、集落形成、迁移和侵袭;②蛋白质印迹结果显示,姜黄素显著增强了吉非替尼逆转 A549／GR 细胞 EMT、诱导凋亡和抑制 AKT 信号传导的能力;③RT-PCR 实验结果显示,上调的 MET 和 AXL 信号可能参与了 A549 细胞对吉非替尼产生抵抗这一过程。上述结果表明,姜黄素可通过抑制 AKT 信号通路逆转 A549／GR 细胞的 EMT,有效增强细胞对吉非替尼的敏感性,促进肿瘤细胞凋亡。
张铭慧
,
孙杨
,
张莹
,
张维维
,
谷光宇
,
贾正虎
,
孟洁
,
高森
. 姜黄素通过 AKT 信号通路抑制上皮-间充质转化逆转非小细胞肺癌对吉非替尼的耐药性[J]. 天津师范大学学报（自然科学版）, 2026
, 46(2)
: 1
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DOI: 10.19638/j.issn1671-1114.20260201
In order to investigate the mechanism of curcumin in reversing the resistance of non-small cell lung cancer to gefitinib,which is a kind of anticancer drug,and thus improve the efficacy of gefitinib,the A549 cell line was used as the experimental cell,and the gefitinib-resistant A549（A549／GR）cell line was successfully established.A549／GR cell line was divided into four treatment groups:control group,gefitinib group,curcumin group,and a combination group of gefitinib and curcumin.Cell Counting Kit-8（CCK-8）,colony formation,transwell,and flow cytometry were used to eval- uate the cell viability,colony formation capacity,migration,invasion,and apoptosis of A549 and A549／GR cells,respec- tively.The protein expression related to apoptosis,epithelial-mesenchymal transition（EMT）,and AKT signaling was studied using Western blot experiment,and the expression level of MET and AXL genes in A549 and A549／GR cells was de- tected by RT-PCR experiment.The results were as follows:①The combination of gefitinib and curcumin had synergistic effects,which enhanced chemosensitivity and cell apoptosis,and inhibited cell proliferation,colony formation,migration and invasion at the same time;②Western blot showed that curcumin significantly enhanced the ability of gefitinib to reverse EMT of A54／GR cells,induce apoptosis and inhibit AKT signaling;③RT-PCR experimental results showed that the up-reg- ulated MET and AXL signaling might be involved in the process of A549 cells resistant to gefitinib.In conclusion,the above results showed that curcumin could reverse the EMT of A549／GR cells through inhibiting the AKT signaling pathway,effec- tively enhance the sensitivity of cells to gefitinib,and promote the apoptosis of tumor cell.
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