胸苷磷酸化酶对胆管癌肿瘤侵袭性和 5-氟尿嘧啶敏感性的影响。
Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma.
机构信息
Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
出版信息
World J Gastroenterol. 2010 Apr 7;16(13):1631-8. doi: 10.3748/wjg.v16.i13.1631.
AIM
To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA).
METHODS
A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines.
RESULTS
TP mRNA and protein expression were decreased by 87.1% + or - 0.49% and 72.5% + or - 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil.
CONCLUSION
Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.
目的
通过小干扰 RNA（siRNA）来评估胸苷磷酸化酶（TP）在胆管癌中的作用。
方法
使用 siRNA 瞬时敲低具有天然高内源性 TP 的人胆管癌细胞系 KKU-M139 中的 TP 表达。在 TP 敲低和野生型细胞系中检测细胞生长、迁移、体外血管生成、细胞凋亡和细胞毒性。
结果
与对照细胞相比，TP mRNA 和蛋白表达分别降低了 87.1%+或-0.49%和 72.5%+或-3.2%。抑制 TP 显著降低了 KKU-M139 的迁移，并抑制了人脐静脉内皮细胞的迁移和管形成。siRNA 还降低了 TP 抵抗缺氧诱导细胞凋亡的能力，而抑制 TP 降低了 KKU-M139 对 5-氟尿嘧啶的敏感性。
结论
抑制 TP 可能有助于减少胆管癌中依赖血管生成的生长和迁移，但可能会降低对 5-氟尿嘧啶化疗的反应。
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