- 作者: 周鳳英; 雷永耀; 戚謹文; 陳榮楷
- 作者服務機構: 國立清華大學原子科學技術發展中心; 台北榮民總醫院; 中央研究院生物醫學研究所
- 中文摘要: 肝癌為台灣常見之癌病,迫切需要新的有效治療方法。最近雖有以放射性碘化罌粟油處理肝癌之報導;其對病人之毒性低,結果相當令人鼓舞。但碘化罌粟油對肝癌細胞之標的及積聚機制尚不十分清楚。本研究探討碘化罌粟油之細胞效應及放射性碘化罌栗油對肝癌細胞之毒性。 研究中以人類肝癌HepG2細胞加入碘化罌粟油培養,以未處理之HepG2細胞做對照組,細胞形態之改變以光學及電子顯微鏡做觀察;HepG2細胞對碘化罌粟油之攝入及積聚則以位像差顯微術及中子活化法分析。在HepG2細胞中加入0.12μCi至120μCi不同活性之放射性碘化罌粟油培養,放射性碘化罌粟油之細胞毒性以其殘存分數評估之;細胞形態之變化以光學顯微鏡檢驗。 結果發現HepG2細胞可以內吞噬大量的碘化罌粟油,並長期積聚於細胞內而使細胞形成許多向外突起之小泡。放射性碘化罌粟油對HepG2細胞具高毒性,其劑量反應曲線相當陡,造成半致死量所需之施給之放射碘活性為1.2μCi(合480rads)。 放射性碘化罌粟油對HepG2細胞毒性,包括導致多形性綑胞之形成、細胞增大及核質比例增加,細胞核之數量增多且增大、核周圍部份之細胞質中形成空泡、多核仁,分解碎裂成環狀之核仁亦有所見。我們的研究結果顯示,肝腫瘤細胞可以主動攝入碘化罌粟油,並且長期積聚於細胞內。放射性碘化罌粟油具高細胞胞毒性,可以有效處理HepG2細胞。這些結果在未來增進肝癌病人處理之研究上,應具臨床重要性。
- 英文摘要: Hepatoma is a common cancer in Taiwan. New effective treatment for hepatoma patients is urgentlyneeded. Encouraging results of I-131-lipiodol treatment for hepatoma with minimal toxicity have beenrecently reported. The mechanism of lipiodol targeting and retention by hepatoma are not well understood.The cellular interaction of lipiodol and the cytotoxic effects of I-131-lipiodol on hepatoma cells were in-vestigated in this study. HepG2 cells were cultured with lipiodol, and untreated HepG2 cells were used asthe control. Changes of cellular morphology were accessed by light and electron microscopy. The uptakeand retention of lipiodol by HepG2 cells were studied by phase contrast microscopy and neutron activationanalysis. HepG2 cells were cultured with I-131-lipiodol varying from 0.12 μCi to 120 μCi. The cytotoxiceffect of 1-131-lipiodol was evaluated by the surviving fraction of HepG2 cells. Changes in cellular mor-phology was examined by light microscopy. Results indicated that HepG2 cells were capable of active uptake of large amounts of lipiodol byendocytosis and prolonged intra-cellular retention associated with the formation of many bulging cyto-plasmic extensions. I-131-lipiodol was highly cytotoxic to HepG2 cells. There was a steep dose responserelationship, and the effective dose (LD5o) was 1.2 μCi (480 rads). The cytotoxic effects of 1-131-lipiodolwere associated with pleomorphism of HepG2 cells, an increase in cell size and nuclear-cytoplasmic ratio,an increase in the size and number of nuclei, and vacuolation of the cytoplasm around the nuclear regions.Multiple nucleoli, fragmentation and segregation and ring shaped changes of nucleoli were also observed. In conclusion, hepatoma cells are capable of active uptake of lipiodol and retention inside the cellsfor prolonged periods of time. 1-131-lipiodol is highly cytotoxic and effective for the treatment of HepG2cells. These results should have major clinical significance in the development of future research in theimprovement of treatment of hepatoma patients.
- 中文關鍵字: I-131-lipiodol; cytotoxic effects; hepatoma cells.
- 英文關鍵字: --