肿瘤防治研究2026，Vol.53Issue(7)：516-522,7.DOI:10.3971/j.issn.1000-8578.2026.25.0898
自噬流在甲状腺髓样癌化疗抵抗中的作用及氯喹联合多柔比星的增敏效应研究
Role of Autophagy Flux in Chemoresistance of Medullary Thyroid Carcinoma and Sensitizing Effect of Chloroquine Combined with Doxorubicin
摘要
Abstract
Objective To investigate the role of cellular autophagy in medullary thyroid carcinoma(MTC)under doxorubicin(DOX)-induced stress and chemoresistance and to evaluate the synergistic antitumor effect of combining the autophagy inhibitor chloroquine(CQ)with DOX.Methods The human MTC cell line TT was used as an in vitro model and assigned to four groups:control,DOX,CQ,and DOX+CQ combination.Autophagy flux was assessed by Western blot analysis of LC3-Ⅱ protein expression,whereas autophagic structures were observed through transmission electron microscopy(TEM).An MTC xenograft model was established in nude mice,and tumor-bearing mice were randomly allocated to corresponding treatment groups.Tumor growth volume and weight were monitored,and autophagy levels in tumor tissues were detected.Results In vitro experiments showed that DOX treatment considerablyincreased LC3-Ⅱ levels,indicating autophagy induction.The combination of DOX and CQ led to further LC3-Ⅱ accumulation,and TEM revealed numerous undegraded autophagosomes and abnormal autolysosomes,confirming the successful blockade of autophagic flux.In vivo,the DOX+CQ combination therapy inhibited tumor growth significantly more effectively than any single-agent treatment(tumor inhibition rate:60.0%,P<0.01)without causing considerable systemic toxicity.Marked accumulation of LC3-Ⅱ in tumor tissues from the comb-ination group indicated the effective inhibition of autophagic flux in vivo.Conclusion Functional autophagy flux is a key mechanism underlying DOX chemoresistance in MTC.CQ can effectively reverse this resistance by blocking autophagic flux,and its combination with DOX exhibits a considerable synergistic antitumor effect.These findings suggest a promising therapeutic strategy for the management of advanced MTC.关键词
甲状腺髓样癌/细胞自噬/氯喹/多柔比星/化疗增敏Key words
Medullary thyroid carcinoma/Autophagy/Chloroquine/Doxorubicin/Chemosensitization分类
医药卫生引用本文复制引用
陈雅婷,王雪玉,王玉龙..自噬流在甲状腺髓样癌化疗抵抗中的作用及氯喹联合多柔比星的增敏效应研究[J].肿瘤防治研究,2026,53(7):516-522,7.基金项目
国家自然科学基金(82372875)National Natural Science Foundation of China(No.82372875) （82372875）
