Yang Mei-Due, Wu Cheng-Chung, Chiou Shiow-Her, Chiu Chang-Fang, Lin Tze-Yi, Chiang I-Ping, Chow Kuan-Chih
Department of Surgery, China Medical College Hospital and Institute of Medical Science, China Medical College, Taichung, Taiwan.
Oncol Rep. 2003 Mar-Apr;10(2):271-6.
Dihydrodiol dehydrogenase (DDH) is one of the major enzymes catabolizing polycyclic aromatic hydrocarbons in the liver. Although four DDH isoforms have been detected in the normal liver, only DDH1 and DDH2 have been detected in cancer cells of lung and esophagus. Moreover, the available information about hepatic pathophysiological regulation of DDH expression is limited. Therefore we addressed the question of DDH expression in patients with liver disorders, in particular, patients with hepatocellular carcinoma (HCC). Expression of DDH1/2 was determined by immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR) in 52 patients with resected HCC. DDH1/2 expression was detected in 31 (59.6%) of 52 pathological sections. Frequency of DDH1/2 expression was significantly higher in patients with tumor size >2 cm, and in those who had early local recurrence. In addition to the tumor size and frequency of local recurrence, our results further indicated that expression of DDH1/2 was correlated with those of cyclooxygenase 2 (COX-2), interleukin-6 (IL-6), microsomal epoxide hydrolase (mEpH) and soluble epoxide hydrolase (sEpH) in HCC patients. Interestingly, the expression of DDH1/2 was found inversely correlated with that of glutathione S-transferase (GST) and NADPH p450 reductase (NPR). In conclusion, these results indicate that DDH expression was significantly decreased in about 40% of HCC patients. However, in the bordering non-neoplastic region of liver DDH1/2 expression increased, and the increased DDH1/2 expression correlated with tumor size and the disease progression.
二氢二醇脱氢酶（DDH）是肝脏中分解代谢多环芳烃的主要酶之一。尽管在正常肝脏中已检测到四种DDH同工型，但在肺癌和食管癌的癌细胞中仅检测到DDH1和DDH2。此外，关于DDH表达的肝脏病理生理调节的现有信息有限。因此，我们研究了肝脏疾病患者，特别是肝细胞癌（HCC）患者中DDH的表达问题。通过免疫组织化学、免疫印迹和逆转录聚合酶链反应（RT-PCR）测定了52例接受手术切除的HCC患者中DDH1/2的表达。在52个病理切片中的31个（59.6%）中检测到DDH1/2表达。肿瘤大小>2 cm的患者以及早期局部复发的患者中，DDH1/2表达频率显著更高。除了肿瘤大小和局部复发频率外，我们的结果进一步表明，HCC患者中DDH1/2的表达与环氧合酶2（COX-2）、白细胞介素6（IL-6）、微粒体环氧化物水解酶（mEpH）和可溶性环氧化物水解酶（sEpH）的表达相关。有趣的是，发现DDH1/2的表达与谷胱甘肽S-转移酶（GST）和NADPH p450还原酶（NPR）的表达呈负相关。总之，这些结果表明，约40%的HCC患者中DDH表达显著降低。然而，在肝脏的毗邻非肿瘤区域，DDH1/2表达增加，且增加的DDH1/2表达与肿瘤大小和疾病进展相关。
