攝護腺癌對化學治療的效果不佳，主要是因為攝護腺癌細胞對大部分的化療藥物會產生抗藥性。先前有文獻研究發現，許多癌症對於化療藥物的抗藥性以及病程的進展與醛酮還原?1C (aldo-keto reductase 1C，AKR1C) 的表現有關係。因此本論文研究的目的是探討攝護腺癌中醛酮還原?1C (aldo-keto reductase 1C，AKR1C) 的表現與抗藥性以及病情發展的相關性。
從1996年一月到2005年十二月之間，我們總共收集了86組被診斷為攝護腺癌的病理組織標本。同時也從美國取得了31組攝護腺癌的組織切片微陣列 ( tissue microarray)，用來比較台灣和美國兩個國家攝護腺癌病患之間的差異性。我們採用免疫組織化學法 (immunohistochemistry) 來測量組織切片中 aldo-keto reductase family 1, member C2 (AKR1C2) 的表現。 AKR1C2 經由二維免疫點墨分析法 (two-dimensional immunoblotting assay) 和反轉錄聚合?連鎖反應 (reverse transcription-polymerase chain reaction；RT-PCR) 的去氧核糖核酸定序分析 (DNA sequencing) 來檢測確定。由上述的分析研究，證實了攝護腺癌中 AKR1C2 的存在，我們得以分析統計 AKR1C2 的表現與臨床病理的相關性。另外我們也探討攝護腺癌細胞的敏感性雄性激素細胞 (androgen-sensitive prostatic cancer cells) 以及攝護腺癌細胞非敏感性雄性激素細胞 (androgen-insensitive prostatic cancer cells) 的抗藥性與AKR1C2濃度的關聯性。
關於我們的研究資料，在台灣方面，攝護腺癌的86組檢體當中有77組檢體被測出含有過度表現AKR1C2的比率為89.5% ; 而美國方面的31組檢體中有28組檢體被檢測出含有過量的 AKR1C2，比率高達為90.3%。對於攝護腺癌高濃度 AKR1C2 的存在情形，以台灣和美國這兩個國家的檢體實驗比較後其結果並無差異。另外我們的實驗顯示 AKR1C2 以及前列腺素 prostaglandin F2α(PGF2α) 的表現增加時，會增進細胞的保護而產生抗藥性。
綜合以上的研究結果，我們得到以下的結論：AKR1C2 的表現過高與攝護腺癌的疾病進展和抗藥性有相關。
Prostatic cancer is resistant to chemotherapy. Expression of aldo-keto reductase 1C (AKR1C) has been associated with drug resistance and disease progression in several cancers. The aim was to investigate the relationship between AKR1C expression and disease progression in prostatic cancer.
From January 1996 to December 2005, 86 pathological samples were collec- ted from patients with prostatic cancer. A tissue microarray containing 31 prostatic cancers from American patients was used for comparison between Chinese and American patients. Using immunohistochemistry, aldo-keto reductase family 1, member C2 (AKR1C2) expression was assessed in tissue sections. The AKR1C2 was determined by two-dimensional immunoblotting and DNA sequencing of reverse transcriptase-polymerase chain reaction products. The relationship between AKR1C2 expression and clinicopathological variables was statistically analysed. In vitro, the association between AKR1C2 expression and drug resistance was investigated in androgen- sensitive and androgen-insensitive prostatic cancer cells. DNA sequencing and two-dimensional immunoblotting showed that prostatic cancer expressed AKR1C2. It was overexpressed in 77 of 86 (89.5%) Chinese and in 28 of 31 (90.3%) American samples. AKR1C2 expression was not significantly different between Chinese and American prostatic cancer patients. In vitro, increased expression of AKR1C2 and prostaglandin F2a correlated with cytoprotection against anticancer drugs and lycopene.
Conclusion: overexpression of AKR1C2 is associated with disease progression in prostatic cancer.
