Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation.
Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation.
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二甲双胍通过PECAM-1介导的MRPs下调逆转受照射的CNE-1人鼻咽癌细胞中顺铂的耐药性
DOI：
10.7150/ijms.48635
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发表时间：
2020
影响因子：
3.6
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Sun Y;Chen X;Zhou Y;Qiu S;Wu Y;Xie M;Zhu G;Liang S;Li H;Zhou D;Ju Z;Wang F;Han F;Wang Z;Wang R
目的：目的：探讨逆转鼻咽癌细胞株CNE-1辐射后耐药性的方法，为寻找一种高效低毒的治疗方法提供新的思路。研究方法：300戈伊照射CNE-1人鼻咽癌细胞后，分别用顺铂或二甲双胍单药或联合用药。MTT法和流式细胞仪检测细胞活力和凋亡。Western blot和RT-PCR检测不同药物作用后细胞蛋白和mRNA的表达。结果如下：结果表明，单药二甲双胍能够抑制照射后的CNE-1细胞的肿瘤生长并诱导细胞凋亡，并且与顺铂也表现出协同作用。此外，二甲双胍下调PECAM-1的表达，这可能会调节多药耐药相关蛋白（MRP）的表达，导致辐射CNE-1细胞的顺铂耐药性。泛MRP抑制剂丙磺舒可逆转放疗引起的顺铂耐药。结论：由于其对PECAM-1的独立作用，二甲双胍对照射后的CNE-1细胞具有独特的抗增殖作用。为克服晚期鼻咽癌放疗后顺铂耐药提供了一种新的治疗选择。
Objective: To explore a way to reverse the drug resistance for irradiated CNE-1 human nasopharyngeal carcinoma cells and try to develop a new high efficacy with low toxicity therapeutic approach. Methods: 300 Gy irradiated the CNE-1 human nasopharyngeal carcinoma cells, and then treated with single-agent cisplatin or metformin, or combination of both drugs. MTT assay and FCM were applied to detect cell viability and apoptosis. Western blot and RT-PCR were used to characterize the protein and mRNA expression after various drug administrations. Results: The results presented single-agent metformin was capable of arresting the tumor growth and inducing apoptosis in irradiated CNE-1 cells and also demonstrated a synergy effect with cisplatin. Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells. A pan-MRP inhibitor, probenecid, can resecure cisplatin resistance leading by radiation. Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells. It would be a new therapeutic option to conquer cisplatin resistance for advanced NPC patients after radiotherapy.
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发表时间：
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