Human Telomerase Reverse Transcriptase (hTERT): A Target Molecule for the Treatment of Cisplatin-resistant Tumors
Human Telomerase Reverse Transcriptase (hTERT): A Target Molecule for the Treatment of Cisplatin-resistant Tumors
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DOI：
10.3343/kjlm.2008.28.6.430
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发表时间：
2008-12-01
影响因子：
--
通讯作者：
Lee, Hee Gu
中科院分区：
文献类型：
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作者：
Park, Yuk Pheel;Kim, Kwang Dong;Lee, Hee Gu
背景资料：人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）是端粒酶活性和肿瘤进展所必需的催化酶。端粒酶抑制或失活增加细胞对紫外线照射、DNA损伤剂、酪氨酸激酶抑制剂伊马替尼的敏感性。和药理学抑制剂，如BIBR 1532。hTERT与细胞凋亡有关。部分患者在抗癌药物治疗过程中出现耐药，癌细胞获得抗凋亡机制。方法采用Western blotting和TRAP方法检测hTERT蛋白水平和活性与耐药的关系。为了研究hTERT是否参与肿瘤细胞的耐药性，我们用小干扰RNA（siRNA）瞬时降低T24/R2细胞中的TERT水平。结果：hTERT敲低增加Bax向线粒体的转位和细胞色素C向胞浆的释放。Caspase抑制剂，特别是Z-VAD-FMK，挽救了这一现象，提示hTERT的稳定性或表达可能受到caspase活性的调节。结论：这些数据提示hTERT可能是耐药肿瘤治疗的靶分子，（Korean J Lab Med 2008：28：430-7）
Background : Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme that is required for telomerase activity (TA) and cancer progression. Telomerase inhibition or inactivation increases cellular sensitivity to UV irradiation, DNA-damaging agents, the tyrosine kinase inhibitor, imatinib. and pharmacological inhibitors, such as BIBR1532. hTERT is associated with apoptosis. Some patients show drug-resistance during anti-cancer drug treatment and the cancer cell acquire anti-apoptotic mechanism. Therefore, we attempted to study correlation between hTERT and drug-resistance.Methods To study the correlation between protein level and activity of hTERT and drug-resistance, Western blotting and telomerase repeat amplification protocol (TRAP) assays were performed. To investigate whether hTERT contributes to drug resistance in tumor cells, we transiently decreased TERT levels using small interfering RNA (siRNA) in T24/R2 cells.Results : hTERT knockdown increased Bax translocation into the mitochondria and cytochrome C release into the cytosol. Caspase inhibitors, especially Z-VAD-FMK, rescued this phenomenon, suggesting that the stability or expression of hTERT might be regulated by caspase activity.Conclusions : These data suggest that hTERT might be a target molecule for drug-resistant tumor therapy, (Korean J Lab Med 2008:28:430-7)