LHRH Receptor Monoclonal Antibody 4F3B10 Induces Apoptosis of HeLa Cells
LHRH Receptor Monoclonal Antibody 4F3B10 Induces Apoptosis of HeLa Cells
复制标题
LHRH受体单克隆抗体4F3B10诱导HeLa细胞凋亡
DOI：
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Guoli Zhang
中科院分区：
文献类型：
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作者：
Xin Deng;Guoli Zhang
背景：肿瘤组织中过度表达的细胞受体是开发针对癌细胞的特异性靶向药物的有效靶点。这些药物对靶器官的特异性高，对患者的副作用小。促黄体生成素释放激素受体（LHRHR）在一些实体肿瘤中有过表达的报道。方法：利用基因表达谱筛选HeLa细胞中具有拮抗剂4F3B10作用的差异表达基因，并通过生物信息学分析差异表达基因之间的关系。采用CCK-8法和流式细胞术检测4F3B10诱导HeLa细胞的增殖和凋亡情况。结果：CCK-8和流式细胞术显示4F3B10抑制HeLa细胞增殖，诱导HeLa细胞凋亡呈剂量依赖性。此外，4F3B10抑制HeLa细胞G1期的细胞周期进程。微阵列分析发现，4F3B10处理的HeLa细胞与未处理的HeLa细胞之间存在2329个差异表达基因。编码Caspase6、Caspase8、Caspase10、CFLAR、FASLG、IRAK2、PPP3CB、PPP3CC、PPKAR2A和TNFRSF10D的凋亡基因在4F3B10处理的HeLa细胞中上调。结论：LHRHR 4F3B10单克隆抗体在HeLa癌细胞中的抗癌作用，包括对细胞周期进程、增殖和诱导凋亡的显著作用。我们的研究结果确定了几个关键的凋亡差异表达基因，并为进一步研究LHRHR的分子机制提供了支持。
Background: Cellular receptors that overexpressed in the tumor tissues are effective targets for the development of specific targeting agents for cancer cells. These drugs have high specificity for target organs and reduced side effects in patients. Overexpression of luteinizing hormone releasing hormone receptor (LHRHR) has been reported in some solid tumors. Here, we investigated the effect and mechanism of the LHRHR monoclonal antibody 4F3B10 on HeLa cells..Methods: Gene expression profiles were utilized to screen the differentially expressed genes in HeLa cells with the effects of antagonist 4F3B10 and analyze the relation among the differentially expressed genes by bioinformatics analysis. CCK-8 assays and flow cytometry were used for detecting the proliferation and apoptosis of HeLa cells induced by 4F3B10..Results: CCK-8 assays and flow cytometry showed that 4F3B10 inhibited proliferation and induced apoptosis of HeLa cells in a dose-dependent manner. Furthermore, 4F3B10 inhibited the cell cycle progression of HeLa cells at G1 phase. Microarray analysis identified 2329 differentially expressed genes between HeLa cells treated with 4F3B10 and untreated cells. Apoptotic genes encoding Caspase6, Caspase8, Caspase10, CFLAR, FASLG, IRAK2, PPP3CB, PPP3CC, PPKAR2A and TNFRSF10D were upregulated in HeLa cells treated with 4F3B10. RTqPCR was performed to validate the microarray findings..Conclusions: Here we demonstrate the anti-cancer effects of the LHRHR 4F3B10 monoclonal antibody in HeLa cancer cells, including significant effects on cell cycle progression, proliferation and induction of apoptosis. Our results identified several key differentially expressed apoptotic genes and support further study of the molecular mechanism of LHRHR.