Department of Otolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Anticancer Drugs. 2010 Apr;21(4):381-8. doi: 10.1097/CAD.0b013e3283363980.
Drug resistance often causes failure of chemotherapy in nasopharyngeal carcinoma (NPC). Thus, it is of great importance to overcome drug resistance by developing effective reversal therapies. The purposes of this study were to examine whether cisplatin could reverse the taxol-resistant phenotype of NPC cells, and to evaluate the role of the taxol-resistant gene (TXR1)/thrombospondin (TSP1) pathway in the reversal of taxol resistance. A drug (taxol)-resistant cell line, CNE-1/taxol, was established from a human NPC cell line, CNE-1. The sensitivity of both CNE-1 and CNE-1/taxol to cisplatin or paclitaxel was detected using the colony formation assay. Apoptotic death was measured by flow cytometry. The expression of the TXR1 and TSP1 was determined by RT-PCR and western blot. The growth inhibition rate in CNE-1/taxol cells in response to taxol was significantly increased when they were pre-treated with low-dose cisplatin. CNE-1/taxol cells were more sensitive to cisplatin than CNE-1 cells when exposed to 300-1500 nmol/l of cisplatin. An approximate seven-fold increase in TXR1 mRNA expression and an 8.9-fold decrease in TSP1 mRNA expression were observed in taxol-resistant cells compared with their parental cells. An 8.7-fold increase in TSP1 mRNA expression was observed in CNE-1/taxol cells exposed to 590 nmol/l of cisplatin for 24 h. An increase in TSP1 protein expression was obtained in a dose-dependent manner after CNE-1/taxol cells were exposed to cisplatin. However, there was no change in TXR1 mRNA expression after both CNE-1 and CNE-1/taxol cells were exposed to cisplatin. We conclude that cisplatin reverses drug resistance through the upregulation of TSP1 downstream of TXR1.
药物耐药性常导致鼻咽癌（NPC）化疗失败。因此，通过开发有效的逆转疗法来克服耐药性非常重要。本研究旨在探讨顺铂是否可以逆转 NPC 细胞的紫杉醇耐药表型，并评估紫杉醇耐药基因（TXR1）/血小板反应蛋白 1（TSP1）通路在逆转紫杉醇耐药中的作用。从人 NPC 细胞系 CNE-1 中建立了一种药物（紫杉醇）耐药细胞系 CNE-1/taxol。通过集落形成试验检测 CNE-1 和 CNE-1/taxol 对顺铂或紫杉醇的敏感性。通过流式细胞术测量细胞凋亡。通过 RT-PCR 和 Western blot 测定 TXR1 和 TSP1 的表达。在低剂量顺铂预处理后，CNE-1/taxol 细胞对紫杉醇的抑制率明显增加。当 CNE-1/taxol 细胞暴露于 300-1500 nmol/L 的顺铂时，其对顺铂的敏感性明显高于 CNE-1 细胞。与亲本细胞相比，紫杉醇耐药细胞中 TXR1 mRNA 的表达增加了约 7 倍，TSP1 mRNA 的表达减少了 8.9 倍。在暴露于 590 nmol/L 顺铂 24 h 的 CNE-1/taxol 细胞中，TSP1 mRNA 的表达增加了 8.7 倍。CNE-1/taxol 细胞暴露于顺铂后，TSP1 蛋白表达呈剂量依赖性增加。然而，在 CNE-1 和 CNE-1/taxol 细胞暴露于顺铂后，TXR1 mRNA 的表达没有变化。我们的结论是，顺铂通过上调 TXR1 下游的 TSP1 逆转药物耐药性。
