本實驗探討 Paclitaxel 對人類肝癌細胞株(HA 22 T/VGH) 的 NAT 基因及 細胞週期的影響。本實驗探討不同濃度 Paclitaxel 對人類肝癌細胞株(HA 22 T/VGH) 細胞中 NAT 的活性及人類肝癌細胞株(HA 22 T/VGH) 細胞胞質液中 NAT 的活性的影響，發現加不同濃度的 Paclitaxel 經 6，12，18，24 小時培養，
可增加 NAT 的活性，且濃度愈高，培養時間愈久，NAT 活性增加就愈明顯。
在 RT-PCR 的實驗中，經由最後的照相結果觀察，發現不同濃度的 Paclitaxel 加在人類肝癌細胞株(HA 22 T/VGH) 細胞，(HA 22 T/VGH)細胞的 NAT1基因 的表現被抑制。可是 Paclitaxel 又會降低人類肝癌細胞株(HA 22 T/VGH) 細胞 胞質液的 NAT 活性，而且 Paclitaxel 對人類肝癌細胞株(HA 22 T/VGH) 細胞 NAT 基因的影響，主要是抑制人類肝癌細胞株(HA 22 T/VGH) 細胞 NAT1基 因的表現(NAT mRNA)。檢測不同濃度的 Paclitaxel 對人類肝癌細胞株(HA 22 T/VGH) 的細胞毒性作用，結果發現濃度越高，細胞的毒殺效果就愈強。其次 由人類肝癌細胞株(HA 22 T/VGH) 細胞經不同濃度 Paclitaxel 處理 24 小時 後，再萃取細胞 DNA 去跑電泳，結果發現 DNA 有出現裂解現象，所以發現 Paclitaxel 造成人類肝癌細胞株 (HA 22 T/VGH) 細胞的死亡方式，不是經由細 胞壞死，而是經由計劃性的細胞死亡。人類肝癌細胞株(HA 22 T/VGH) 細胞 經不同濃度的 Paclitaxel 處理 24 小時後，再經由流式細胞計數儀(FACS)分析 結果顯示，Paclitaxel 會造成人類肝癌細胞株(HA 22 T/VGH) 細胞週期的變
G2/M 期，利用 FAS 分析也間接證明了 Paclitaxel 對人類肝癌細胞株(HA 22 T/VGH) 細胞死亡方式不是經由細胞壞死，而是經由計劃性的細胞死亡。
此結果顯示，Paclitaxel 會增加人類肝癌細胞株(HA 22 T/VGH) 細胞 NAT 活性及抑制人類肝癌細胞株(HA 22 T/VGH) 細胞 NAT1 基因的表現。但是 Paclitaxel 的抗腫瘤作用，是否與 Paclitaxel 能降低人類肝癌細胞株 (HA 22 T/VGH) 細胞 NAT1基因表現有關呢?這待進一步的研究。
在整個細胞中，Paclitaxel 可以促進 NAT 對 2-AF 的乙醯化作用，而此促 進作用與劑量大小有關(dose-dependent)。歸納來說 Paclitaxel 可以且會導致細 胞的計劃性死亡影響人類肝癌細胞株(HA 22 T/VGH)的細胞週期，使細胞週期 停留在 G2/M 期。經由細胞 cyclins 的分析發現，G2 期的停留與 CDK1 –Cyclin B 被 Paclitaxel 抑制有關且與藥物濃度相關聯。
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表 1 常見的化學致癌物
類 別 化 合 物
多 環 芳 香 烴 Polycyclic aromatic hydrocarbons
苯呲? (Benzo [a] pyrene)
二甲基苯並? (dimethylbenzanthracene) 芳香胺 Aromatic amines 2-乙醯氨基笏 (2-Acetylaminofluorene)
N-甲基-4 氨基偶氮苯
(N-methyl-4-aminoazobenzene (MAB) ) 亞硝氨 Nitrosamines 二甲基亞硝氨 (Dimethylnitrosamine)
二乙基亞硝氨 (diethylnitrosamine)
各種藥物 Various drugs 烷基化藥劑(Alkylating agents 二乙基乙烯雌酚 (例如, cyclophosphamide), diethylstibestrol 自 然 界 化 合 物 Naturally occurring
compounds
放線菌素(Dactinomycin, 黃麴毒素 aflatoxin B1)
無機化合物 Inorganic compounds 砷(Arsenic) 石棉(asbestos) 鈹(beryllium) 鎘(cadmium) 鉻(chromium)
表 2 不同濃度的 Paclitaxel 對肝癌細胞株 HA 22T/VGH NAT 活性的影響
表 2 不同濃度的 Paclitaxel 對肝癌細胞株 HA 22T/VGH NAT 活性的影響