腺病毒基因替代疗法（p14ARF和p16INK4A）对人恶性间皮瘤细胞的抗肿瘤疗效比较分析
A comparison analysis of anti-tumor efficacy of adenoviral gene replacement therapy (p14ARF and p16INK4A) in human mesothelioma cells.
作者信息
Yang Cheng-Ta, You Liang, Lin Yu-Chin, Lin Chun-Liang, Mccormick Frank, Jablons David M
机构信息
Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
出版信息
Anticancer Res. 2003 Jan-Feb;23(1A):33-8.
BACKGROUND
Tumor suppressor genes encode critical cell cycle regulatory proteins that are frequently mutated or deleted in cancer and, therefore, are important candidates for cancer treatment based on gene replacement strategies.
MATERIALS AND METHODS
We evaluated and compared the relative potential therapeutic efficacy of p14ARF and p16INK4A expressed in adenoviral vectors (Adp14ARF and Adp16INK4A, respectively) in three human mesothelioma cell lines.
RESULTS
The cytotoxic effects of expressed p16INK4A were significantly greater than that of p14ARF in both H28 and H2052 cells. Cell cycle G1 arrest occurred earlier with Adp16INK4A treatment than Adp14ARF (24 hours vs. 48 hours, respectively). Although both Adp14ARF and Adp16INK4A inhibited cell proliferation significantly and were potentiated by chemotherapy, Adp16INK4A appeared more potent.
CONCLUSION
Our results suggest that adenoviral gene-based therapy, especially using Adp16INK4A-based strategy, may be effective in the treatment of human mesothelioma.
背景
肿瘤抑制基因编码关键的细胞周期调节蛋白，这些蛋白在癌症中经常发生突变或缺失，因此是基于基因替代策略的癌症治疗的重要候选对象。
材料与方法
我们评估并比较了腺病毒载体（分别为Adp14ARF和Adp16INK4A）中表达的p14ARF和p16INK4A在三种人恶性间皮瘤细胞系中的相对潜在治疗效果。
结果
在H28和H2052细胞中，表达的p16INK4A的细胞毒性作用明显大于p14ARF。Adp16INK4A处理比Adp14ARF更早出现细胞周期G1期阻滞（分别为24小时和48小时）。虽然Adp14ARF和Adp16INK4A均显著抑制细胞增殖且化疗可增强其作用，但Adp16INK4A似乎更有效。
结论
我们的结果表明，基于腺病毒基因的治疗，尤其是使用基于Adp16INK4A的策略，可能对人恶性间皮瘤的治疗有效。
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