摘要
核糖体蛋白在多种肿瘤中存在异常表达,通过多种机制影响肿瘤细胞的凋亡、衰老、生长、侵袭、药物和放射治疗抵抗等。核糖体蛋白在肿瘤的表达水平与肿瘤的病理分级,临床分期密切相关,成为肿瘤诊断,治疗和预后判断的潜在指标。核糖体蛋白可以通过磷酸化等修饰,改变其在肿瘤发生发展中的活性和作用方式。核糖体蛋白与化疗药物的作用机制不同,能够调节肿瘤细胞对药物的敏感性,从而以一种低毒、有效的方式逆转肿瘤细胞的多药耐药。通过调控核糖体蛋白进行细胞周期的再分布,将肿瘤的细胞周期阻滞在G0~G1期,减少G2~M期细胞的比例。以参与核糖体蛋白合成的RNA聚合酶Ⅰ蛋白酶等作为靶点间接调控核糖体蛋白的治疗方式,在动物模型中显示出显著的抗肿瘤活性。作用于核糖体蛋白的药物,由于不直接对基因组产生影响,没有明显的细胞毒性,对分化成熟的正常组织细胞的遗传毒性很低,具有更好的靶向性。显而易见,针对核糖体蛋白的肿瘤治疗具有高度特异性,能够有效逆转多药耐药和放射增敏,提供了一种潜在低毒的治疗方式。
Ribosomal protein(RP)is abnormally expressed in various tumors,and affects apoptosis,senescence,growth,invasion,drug and radiation therapy resistance of tumor cells through various mechanisms.The expression level of RP in tumors is closely related to the pathological grade and clinical stage of the tumor,and it becomes a potential indicator for tumor diagnosis,treatment and prognosis.RP can be modified by phosphorylation or the like to change its activity and mode of action in tumor development.The mechanism of action of RP is different from that of chemotherapy drugs,which can regulate the sensitivity of tumor cells to drugs,so as to reverse the multi-drug resistance of tumor cells in a low-toxicity and effective way.By regulating the RP to redistribute the cell cycle,the cell cycle of the tumor is arrested in the G0-G1 phase,reducing the proportion of cells in the G2-M phase.The RNA polymerase I protease involved in RP synthesis was used as a target to indirectly regulate the treatment of RP,and showed significant antitumor activity in animal models.The drug acting on RP has no obvious cytotoxicity due to its direct effect on the genome,and has low genotoxicity to the differentiated mature normal tissue cells and has better targeting.Obviously,tumor treatment for RP is highly specific and can effectively reverse multidrug resistance and radio-sensitization,providing a potentially low-toxic treatment.
作者
袁飞
王树斌
YUAN Fei;WANG Shu-bin(Clinical Laboratory,Baotao Central Hospital,Baotao 014040,Inner Mongolia,China;Department of Oncology,Baotao Central Hospital,Baotao 014040,Inner Mongolia,China;Cancer prevention and control institution of Baotou medical college,Baotao 014040,Inner Mongolia,China;Baotou clinical medical college of Inner Mongolia Medical University,Baotao 014040,Inner Mongolia,China)
出处
《肿瘤代谢与营养电子杂志》
2019年第1期116-119,共4页
Electronic Journal of Metabolism and Nutrition of Cancer
关键词
核糖体蛋白
恶性肿瘤
治疗
The ribosomal protein family
Malignant tumor
Therapy
