hdm -2靶向肽PNC-27可杀死宫颈癌细胞,但不能杀死正常宫颈细胞。

IF 1 4区 医学 Q4 MEDICAL LABORATORY TECHNOLOGY
Patryck K Krzesaj, Shabnam Seydafkan, Anna I Miller, Hui Ting Chen, Prem Premsrirut, Alfred Shim, Steven Mcglinchey, Ehsan Yazdi, Paul Brandt-Rauf, Miriam Silberstein, Gholamali Jahari, Richard D Feinman, Matthew R Pincus
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引用次数: 0

摘要

目的:研究发现肽PNC-27能杀伤多种不同的内胚层实体组织和造血癌细胞,但对正常细胞无杀伤作用。其机制包括与HDM-2蛋白的结合,HDM-2蛋白在癌细胞膜上表达,但在正常(未转化)细胞中不表达。我们当前研究的目的是确定1)PNC-27是否对宫颈鳞状上皮细胞致死,但对未转化的宫颈鳞状细胞不致死;2)膜结合HDM-2是否在宫颈癌细胞中唯一表达;3) HDM-2在不同类型的防腐剂溶液中检测是否稳定。方法:测定PNC-27与人宫颈鳞癌细胞系HTB-35(也称为SiHa细胞)和未转化人宫颈鳞癌细胞系PCS-480孵育的剂量反应曲线。用MTT和LDH释放法测定细胞活力。最后,利用多克隆抗HDM-2抗体,采用槽型印迹和流式细胞术检测HDM-2的膜表达。结果:PNC-27对人HTB-35宫颈癌鳞状上皮细胞系具有低剂量(IC50=12.4 μM)的细胞毒性,但对正常人PCS-480细胞系没有细胞毒性。我们发现HTB-35细胞在细胞培养和酒精防腐剂溶液中都在其膜中表达高水平的HDM-2蛋白,而正常的PCS-480细胞则没有。与先前的结果一致,数据表明宫颈癌细胞在其膜中表达HDM-2,这是PNC-27的靶标。结论:由于HDM-2在宫颈鳞膜上的独特表达,PNC-27对宫颈鳞癌无杀伤作用。因此,PNC-27可能是一种有效的抗癌药物。我们的研究结果进一步表明,在细胞培养基和酒精保存液中,膜结合的HDM-2在宫颈癌细胞上的表达是稳定的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HDM-2-Targeting Peptide PNC-27 Kills Cervical Cancer Cells but not Normal Cervical Cells.

Objective: The peptide PNC-27 has been found to kill many different endodermal solid tissue and hematopoietic cancer cells but has no effect on normal cells. The mechanism involves binding to the HDM-2 protein, which is expressed in the membranes of cancer cells but not in normal (untransformed) cells. Our objectives in the current study are to determine 1) if PNC-27 is lethal to squamous cervical epithelial cancer cells but not to untransformed squamous cervical cells; 2) if membrane-bound HDM-2 is expressed uniquely in cervical cancer cells; and 3) whether HDM-2 is stable for detection in different types of preservative solutions.

Methods: We determined dose response curves for incubation of PNC-27 with the human squamous cervical cancer cell line HTB-35 (also called SiHa cells) and with the untransformed human squamous cervical cell line, PCS-480. Cell viability was determined using the MTT and LDH release assays. Finally, slot blots and flow cytometry were used to determine membrane expression of HDM-2 using a polyclonal anti-HDM-2 antibody.

Results: We found that PNC-27 is cytotoxic even at low doses (IC50=12.4 μM) to the human HTB-35 cervical cancer squamous epithelial cell line but not to a counterpart normal human PCS-480 cell line. We found that HTB-35 cells express high levels of HDM-2 proteins in their membranes both in cell culture and in alcoholic preservative solutions but that the normal PCS-480 cells do not. Consistent with previous results, the data suggest that cervical cancer cells express HDM-2 in their membranes and that this is the target for PNC-27.

Conclusions: PNC-27 kills cervical squamous cancer but not normal cervical cells due to the unique expression of HDM-2 in the cervical squamous cell membranes. Thus, PNC-27 may be an effective drug against this cancer. Our results further suggest that the expression of membrane-bound HDM-2 on cervical cancer cells is stable both in cell culture media and in alcoholic preservative fluid.

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来源期刊
Annals of clinical and laboratory science
Annals of clinical and laboratory science 医学-医学实验技术
CiteScore
1.60
自引率
0.00%
发文量
112
审稿时长
6-12 weeks
期刊介绍: The Annals of Clinical & Laboratory Science welcomes manuscripts that report research in clinical science, including pathology, clinical chemistry, biotechnology, molecular biology, cytogenetics, microbiology, immunology, hematology, transfusion medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.
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