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抑制α叶酸受体导致鼻咽癌对紫杉醇耐药性的逆转。

Inhibition of α folate receptor resulting in a reversal of taxol resistance in nasopharyngeal carcinoma.

机构信息

Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Otolaryngol Head Neck Surg. 2012 Feb;146(2):250-8. doi: 10.1177/0194599811426260. Epub 2011 Oct 31.

DOI:10.1177/0194599811426260
PMID:22041223
Abstract

OBJECTIVE

To further determine the role of FOLR1 in taxol resistance of nasopharyngeal carcinoma (NPC) and whether inhibition of FOLR1 expression reverses the taxol-resistant phenotype.

STUDY DESIGN

Correlation study between gene expression and cancer cell survival.

SETTING

University hospital.

SUBJECTS AND METHODS

Three taxol-resistant sub-cell lines with a different resistant index were established from the parental CNE-1 NPC cell line. The correlation between FOLR1 expression and taxol sensitivity was statistically analyzed. Inhibition of FOLR1 expression was carried out by RNA interference and by a FOLR1-specific monoclonal antibody, and taxol sensitivity was examined by colony formation assays. FOLR1 expression was also examined in 72 NPC patient specimens by immunohistochemistry.

RESULTS

The levels of FOLR1 expression were positively and significantly correlated with a taxol resistance phenotype (P < .05). Inhibition of FOLR1 expression resulted in a significantly increased sensitivity of taxol to taxol-resistant NPC cells (P < .05). An increase of FOLR1 expression by gene transfection caused a taxol-resistant phenotype in parental NPC cells. The level of FOLR1 expression was found to be related to clinical stage in NPC tissue samples.

CONCLUSION

These results suggest that FOLR1 plays an important role in taxol resistance of NPC cells.

摘要

目的

进一步确定叶酸受体 1(FOLR1)在鼻咽癌(NPC)紫杉醇耐药中的作用,以及抑制 FOLR1 表达是否能逆转紫杉醇耐药表型。

研究设计

基因表达与癌细胞存活相关性的研究。

设置

大学医院。

受试者和方法

从亲本 CNE-1 NPC 细胞系中建立了 3 个具有不同耐药指数的紫杉醇耐药亚细胞系。统计分析 FOLR1 表达与紫杉醇敏感性之间的相关性。通过 RNA 干扰和 FOLR1 特异性单克隆抗体抑制 FOLR1 表达,并通过集落形成实验检测紫杉醇敏感性。还通过免疫组织化学检测了 72 例 NPC 患者标本中的 FOLR1 表达。

结果

FOLR1 表达水平与紫杉醇耐药表型呈正相关(P<0.05)。抑制 FOLR1 表达可显著增加紫杉醇对紫杉醇耐药 NPC 细胞的敏感性(P<0.05)。通过基因转染增加 FOLR1 表达可导致亲本 NPC 细胞出现紫杉醇耐药表型。在 NPC 组织样本中发现 FOLR1 表达水平与临床分期有关。

结论

这些结果表明,FOLR1 在 NPC 细胞紫杉醇耐药中起重要作用。

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