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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

小分子抑制化合物的PERK依赖信号通路作为大肠癌的有希望的基于目标的治疗方法的使用。

卷 20, 期 3, 2020

页: [223 - 238] 页: 16

弟呕挨: 10.2174/1568009620666200106114826

价格: $65

摘要

背景：结直肠癌是死亡率最高的最常见癌症之一。最新数据报道，小分子抑制剂激活促凋亡的PERK依赖性未折叠蛋白应答信号通路可能构成一种创新的抗癌治疗策略。 目的：在本研究中，我们评估了PERK依赖性未折叠蛋白反应信号通路小分子抑制剂42215对HT-29人结肠腺癌和CCD 841 CoN正常人结肠上皮细胞系的有效性。 方法：通过基于刃天青和乳酸脱氢酶（LDH）的测试评估PERK抑制剂的细胞毒性。通过流式细胞术使用FITC缀合的膜联蛋白V指示凋亡和碘化丙啶指示坏死以及通过比色半胱氨酸天冬氨酸蛋白酶3测定来测量凋亡的细胞死亡。通过使用碘化丙锭染色的流式细胞术测量被测PERK抑制剂对细胞周期进程的影响。通过Western印迹技术检测真核起始因子2α的磷酸化形式的水平。 结果：获得的结果表明，所研究的PERK抑制剂仅对癌细胞具有选择性，因为它以剂量和时间依赖性的方式抑制了它们的生存能力，并诱导了它们的凋亡和G2 / M细胞周期停滞。此外，42215 PERK抑制剂引起了HT-29癌细胞内eIF2α磷酸化的显着抑制。结论：高度选择性的PERK抑制剂可通过激活PERK依赖性未折叠蛋白应答信号通路的促凋亡分支来提供突破性的抗癌治疗策略。

关键词: PERK，eIF2α，PERK抑制剂，内质网应激，未折叠的蛋白质反应，癌症，细胞凋亡。

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