人结肠癌 H/MDM-2 癌蛋白的分子靶向及其对类结肠上皮源性祖细胞的作用
Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells.
机构信息
Division of Surgical Oncology, Department of Surgery, Drexel University College of Medicine, Philadelphia, PA, U.S.A.
Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, PA, U.S.A.
出版信息
Anticancer Res. 2021 Jan;41(1):27-42. doi: 10.21873/anticanres.14749.
BACKGROUND/AIM: We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells.
MATERIALS AND METHODS
Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD-18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth.
RESULTS
High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue.
CONCLUSION
PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.
背景/目的：我们已经测试了抗癌肽 PNC-27，它通过与癌细胞膜 HDM-2 结合形成孔来杀死癌细胞而不杀死正常细胞，是否能杀死 CD44+结肠癌细胞干细胞。
材料和方法
流式细胞术测定了六种结肠癌细胞系和一种正常细胞系（CCD-18Co）上的 CD44 和 HDM-2 表达。MTT、LDH 释放、膜联蛋白 V 结合和 caspase 3 测定用于评估 PNC-27 诱导的细胞死亡。生物发光成像测量 PNC-27 对体内肿瘤生长的影响。
结果
所有六种肿瘤细胞系中的细胞都有很高的百分比表达 CD44。PNC-27 仅与癌细胞中的膜 HDM-2 共定位，并导致细胞死亡（肿瘤细胞坏死、高 LDH 释放、膜联蛋白 V 阴性和 caspase 3）。在体内，PNC-27 引起肿瘤结节的坏死，但不引起正常组织的坏死。
结论
PNC-27 通过与膜 H/MDM-2 结合，选择性地杀死结肠癌细胞干细胞。
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