中文摘要
先前的研究發現galectin-1(GAL1)是中國倉鼠卵巢細胞 (CHOA)中的一種亞砷酸鈉 (NaAsO2)結合蛋白。GAL1是一種可溶性的b-半乳糖甘結合蛋白，在它的結構上具有六個半胱胺酸的存在。先前研究也發現GAL1大量表現時，會造成亞砷酸鈉在KB細胞內大量的累積。本論文擬利用RNA 干擾技術，進ㄧ步去探討GAL1的表現和三價無機砷在細胞內誘發毒性的關係。本研究發現，利用RNA 干擾技術建立GAL1蛋白表現抑制的3T3 (siGAL1-3T3)和KB (siGAL1-KB)細胞，並不會影響細胞的生長及型態。分別以NaAsO2 處理24小時或以As2O3處理72小時，均可降低三價砷化物對siGAL1-3T3及siGAL1-KB細胞造成的毒性，減少細胞週期中計畫性死亡(apoptosis)和停止於G2/M時期細胞的比例，並降低細胞中砷化物的累積量。此結果証實GAL1能影響三價無機砷排出細胞外，且其表現量與三價無機砷誘發之毒性成負相關。以NaAsO2 或 As2O3處理 3T3、KB及HeLa S3細胞後，內生性的GAL1蛋白表現量隨著三價無機砷濃度上升而有遞減的現象，此一結果顯示GAL1蛋白對砷化物毒性扮演負調控的角色。此外，抑制GAL1表現與鎘(Cadmium)和鎳(Nickel)誘發的毒性並無任何影響，顯示GAL1參與無機砷誘發之毒性具有專一性。從As2O3作為治療藥物的觀點看來，利用降低GAL1表現量，或許可減少As2O3對正常細胞的傷害、及改善As2O3對腫瘤細胞的治療效果。

Previous studies have shown that galectin-1 (GAL1) is an arsenic binding protein in CHOA cells. GAL1 is a member of the S-type (soluble) of animal b-galactoside-binding proteins with six free cysteines in its structure. Over-expression of GAL1 could enhance the accumulation of sodium arsenite (NaAsO2). This thesis further investigates the role of GAL1 in arsenic (principally the trivalent forms (As(III)), sodium arsenite (NaAsO2) and arsenic trioxide (As2O3)-mediated toxicity by RNAi technique. The results showed that silence of GAL1 expression by RNAi has no effect of the cellular morphology and growth, but significantly potentiates As(III)-induced apoptosis or G2/M phase arrest in 3T3 and KB cells exposed to NaAsO2 for 24 hrs or As2O3 for 72 hr. Knock-down of GAL1 expression also reduce the accumulation of arsenic in 3T3 and KB cells expose to NaAsO2 or As2O3. These results indicated that GAL1 silence in KB and 3T3 cells attenuated arsenic-induced toxicity by lowering arsenic accumulation. In addition, NaAsO2 or As2O3 treatment dose-dependently inhibits the expression of GAL1 in 3T3, KB and HeLa S3 cells. These results indicated that GAL1 plays a negative regulator of cell survival under toxic insult of arsenic. Moreover, the expression of GAL1 has no effect on Cadmium- and Nickel-induced cytotoxicity, indicating that As(III)-modulated GAL1 expression involved a specific interaction. In view of the therapeutic effect of As2O3, the targeted inhibition of GAL1 expression can be employed for As2O3–mediated therapeutic applications to decrease its toxicity and improve its anticancer effect for other tumors.

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