以抗氧化劑治療前列腺癌之角色及分子機轉

Therapeutic Roles and Molecular Mechanisms of Antioxidants in Prostate Cancer

平思遠(Szu-Yuan Ping)

指導教授 ： 林信仁 ； 侯自銓

高雄醫學大學/生命科學院/化學系/碩士(2003年)

摘要

前列腺癌在西方社會是第二最常被發現的癌症，僅次於肝癌，而在台灣地區，因為國人飲食習慣的改變，前列腺癌已進入了的十大癌症死因之列到了民國八十六年更已是男性十大死因癌症的第六位。目前對於前列腺癌的治療方式包括了手術、化療及荷爾蒙療法。但是發現部分病人在接受治療後產生了復發的情形，並且對原有荷爾蒙抑制不再敏感。通常此病患有近半會在三年內死亡。根據先前的研究發現在飲食中攝取一些抗氧化劑高含量的食物可降低前列腺癌發生的機率。著眼於此，本實驗選取了在先前已發現可抑制前列腺癌生長的抗氧化劑同時結合數種抗癌藥物去處理細胞抹PC-3和DU145結果發現(1) G0/G1期停滯現象。(2) DNA呈階樣狀(DNA fragmentation，DNA ladder)。(3) 細胞週期中出現apoptotic fragmentation (Sub G1 peak)。(4) 螢光顯微下可見DNA形態改變(DNA Condensation)。以MTT assay 發現抗氧化劑結合抗癌藥物可以增加細胞毒性。以抗癌藥物加抗氧化劑處理前列腺癌細胞DU145結果發現NF-?B signaling pathway被抑制，進而使caspase-3被活化促進細胞凋零，在前列腺癌癌細胞因為PI3 signaling pathway活化導致癌細胞增生，同樣地以結合抗氧化劑和抗癌藥物處理癌細胞後同樣發現Akt signaling pathway被抑制，促進細胞凋零。

關鍵字

前列腺癌 ； 抗氧化劑

並列摘要

Prostate cancer is the second discovered malignant cancer type, it just behind the hepatoma in western society. In Taiwan area, because of the changing of dietary inhabits, the prostate cancer becomes one of ten major cancers to male death. Presently, surgery, chemotherapy and hormone ablation therapy often are used to prostate cancer regimens. However, virtually all patients eventually relapse with a disease that has been termed hormone-refractory or androgen-independent disease, and will be dead in three years mostly. According to some advanced research discovered some food can prevent prostate cancer occurred, which contains several antioxidants. In this study, we choose some compounds which are with higher antioxidant ability and several clinical anticancer drugs to co-treat prostate cancer cell line PC-3 and DU145 which are hormone refractory prostate cancer. Our results showed the combinations of antioxidants and anticancer drugs induce (1) the phenomenon of G0/G1 arrested. (2) DNA ladder occurred. (3) sub-G1 peak increased. (4) DNA condensation. The molecular mechanisms of cytotoxicty, we found that NF-?B signaling pathway and Akt expression were inhibited by these two drugs combination.

並列關鍵字

none

參考文獻

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