通过降低CDK6,Cyclin A,Cyclin E,c-Myc和VEGF基因表达,B-AP15抑制了结肠癌细胞的增殖
Thanet Sophonnithiprasert1, Sasiwan Konjanthet1, Nattanicha Narinnork1
1Biochemistry Unit, Department of Medical Sciences, Faculty of Science, Rangsit University, Pathum Thani, 12000, Thailand.
Naunyn-Schmiedeberg's archives of pharmacology
|March 29, 2025
概括
这项研究确定了抗癌药物B-AP15在结肠癌细胞中的潜在新点. B-AP15表现出显著的细胞毒性和抑制关键的癌症相关基因,表明其治疗潜力.
科学领域:
- 在瘤学瘤学.
- 计算化学计算化学
- 分子生物学分子生物学
背景情况:
- B-AP15 (NSC687852) 正因为其抗癌性质而受到研究.
- 结肠癌仍然是一个重大的健康问题,需要新的治疗策略.
- 了解药物向相互作用对于开发有效的癌症治疗至关重要.
研究的目的:
- 使用in silico方法选B-AP15的潜在标蛋白.
- 为了评估B-AP15在SW620结肠癌细胞上的体外抗癌活性.
- 研究B-AP15对基因表达和细胞增殖的影响.
主要方法:
- 使用in silico分子对接来选20种与结肠癌相关的蛋白质,以寻找潜在的B-AP15标.
- 使用Discovery Studio 2021分析了B-AP15与候选蛋白的结合相互作用.
- 包括MTT,殖民地形成和试蓝在内的体外测试用于评估SW620细胞中的细胞毒性,增殖和抑制.
- 反转录定量聚合酶链反应 (RT-qPCR) 用于分析基因表达变化.
主要成果:
- B-AP15对E2F8,Ras,GSK3B,CDK6和Raf表现出强烈的结合亲和力,结合能量在-10.12~-10.88 kcal/mol之间.
- 拉斯,GSK3B和CDK6与已知的抑制剂共享结合位置,表明了潜在的共同作用机制.
- B-AP15表现出显著的时间和剂量依赖的细胞毒性,降低细胞活力,殖民地形成,并增加细胞抑制.
- 该药物以剂量依赖的方式抑制了CDK6,循环A,VEGF,循环E和c-Myc的表达.
结论:
- B-AP15对SW620结肠癌细胞表现出强大的抗癌活性.
- 该药物的机制涉及抑制关键基因,包括CDK6,Cyclin A,VEGF,Cyclin E和c-Myc.
- 确定了Ras,GSK3B和CDK6等潜在的新型标,需要进一步调查B-AP15的治疗效果.
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