用TATp16INK4a肽处理后，间皮瘤细胞生长和Cdk4活性均受到抑制。
Inhibition of both mesothelioma cell growth and Cdk4 activity following treatment with a TATp16INK4a peptide.
作者信息
Frizelle Sandra P, Kratzke Marian G, Carreon Richard R, Engel Sean C, Youngquist Laura, Klein Mark A, Fourre Laura, Shekels Laurie L, Kratzke Robert A
机构信息
Research Service, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.
出版信息
Anticancer Res. 2008 Jan-Feb;28(1A):1-7.
UNLABELLED
Disruption of the 9p21 locus is common in mesothelioma and leads to loss of both the p16INK4a and the p14ARF gene products. This study tested the hypothesis that reexpression of p16INK4a carried out using the TAT delivery system that carries the protein transduction domain of the HIV TAT will result in mesothelioma cell death.
MATERIALS AND METHODS
A synthetic TATp16INK4a peptide and a charge matched control were transduced into mesothelioma cells in vitro and in vivo. Cells were assayed for Cdk4 inhibition, cell cycle arrest, and cell death.
RESULTS
Treatment of mesothelioma cells with TATp16INK4a for 48 hours resulted in cell death. Apoptosis and G1 cell cycle arrest was also observed. Following transduction of cells with TATp16INK4a there was complete but transient hypophosphorylation of pRb. Similar effects were observed in mesothelioma xenografts.
CONCLUSION
Therapeutic strategies which introduce either TATp16INK4a peptide, or small molecule mimetic, could be an effective strategy for mesothelioma treatment.
未标记
9p21基因座的破坏在间皮瘤中很常见，并导致p16INK4a和p14ARF基因产物均缺失。本研究检验了这样一个假设，即使用携带HIV TAT蛋白转导结构域的TAT递送系统重新表达p16INK4a会导致间皮瘤细胞死亡。
材料与方法
将合成的TATp16INK4a肽和电荷匹配对照在体外和体内转导到间皮瘤细胞中。检测细胞的Cdk4抑制、细胞周期阻滞和细胞死亡情况。
结果
用TATp16INK4a处理间皮瘤细胞48小时导致细胞死亡。还观察到细胞凋亡和G1期细胞周期阻滞。用TATp16INK4a转导细胞后，pRb出现完全但短暂的低磷酸化。在间皮瘤异种移植模型中也观察到类似效果。
结论
引入TATp16INK4a肽或小分子模拟物的治疗策略可能是治疗间皮瘤的有效策略。
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