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首页> 外文期刊>Journal of dermatological science >Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma.
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Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma.

机译：二氢二醇脱氢酶的表达在A431鳞状细胞癌的凋亡和耐药性中起重要作用。

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摘要

BACKGROUND: Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily which may be involved in normal detoxification process of environmental mutagenic hazards like polycyclic aromatic hydrocarbons (PAH). Previous clinical studies have demonstrated the over-expression of DDH in various types of cancers, including cutaneous squamous cell carcinoma (SCC), and its correlation with tumor progression and grave prognosis. OBJECTIVE: To investigate possible mechanisms for DDH's correlation with tumor progression and unfavorable prognosis. METHODS: DDH expression in SCC A431 cell line was examined by quantitative real-time PCR and immunoblotting. RNA interference (RNAi) by transduction with retroviral vector containing DDH-targeting small interfering RNA was employed to inhibit DDH expression by A431 cells. With DDH expression inhibited or not, sensitivity of A431 cells to UVB-induced apoptosis and cytotoxicity of chemotherapeutic agent bleomycin were then examined and compared. RESULTS: DDH was found highly expressed by SCC A431 cells, which was barely detectable in other normal or malignant cutaneous cells, including keratinocytes, fibroblast, and basal cell carcinoma cell line. RNAi Inhibition of DDH expression in A431 cells led to increased sensitivity to UVB-induced apoptosis and cytotoxicity of bleomycin treatment. CONCLUSION: DDH may play important roles in tumor progression of SCC via induction of apoptosis- and drug-resistance.
机译：背景：二氢二醇脱氢酶（DDH）是醛糖酮还原酶超家族的成员，该家族可能参与环境诱变危害（如多环芳烃）的正常排毒过程。先前的临床研究表明DDH在各种类型的癌症（包括皮肤鳞状细胞癌（SCC））中过表达，并且与肿瘤进展和严重预后相关。目的：探讨DDH与肿瘤进展及不良预后相关的可能机制。方法：采用实时荧光定量PCR和免疫印迹法检测SCC A431细胞中DDH的表达。通过用含有靶向DDH的小干扰RNA的逆转录病毒载体转导的RNA干扰（RNAi）来抑制A431细胞DDH的表达。不论是否抑制DDH的表达，然后检查并比较A431细胞对UVB诱导的凋亡的敏感性和化疗药物博来霉素的细胞毒性。结果：DDH被SCC A431细胞高表达，在其他正常或恶性皮肤细胞中几乎检测不到，包括角质形成细胞，成纤维细胞和基底细胞癌细胞系。 RNAi抑制A431细胞中DDH表达导致对UVB诱导的博来霉素处理的细胞凋亡和细胞毒性的敏感性增加。结论：DDH可能通过诱导细胞凋亡和耐药性在SCC肿瘤进展中发挥重要作用。

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