CAJ | 학술논문

细胞周期是细胞生命活动的基本过程，它控制着细胞从静止期转向生长增殖期。细胞周期蛋白依赖激酶（Cdks）和细胞周期蛋白（Cyclins）是整个细胞周期调控机制中的核心分子。细胞周期调控异常与细胞癌变密切相关，90％以上的肿瘤，尤其是胶质瘤和软组织肉瘤中 Cdks 都有过度表达。进一步分析指出，Cdks 和 Cyclins 被作为治疗肿瘤的关键靶点，它们受抑制时能导致肿瘤细胞的死亡，抑制 Cdks 还能阻滞 Cyclins 转录。Ⅰ期临床研究提示，细胞周期素蛋白激酶抑制剂（CDKIs）有较高的安全性；Ⅱ期临床研究提示，CDKIs 联合细胞毒性化疗药物作用肿瘤细胞有更好的前景，且 CDKIs 的使用剂量和时间顺序决定着其最佳使用效果。本文阐述了 Cdks 和 Cyclins在肿瘤细胞周期中的表达，对 Flavopiridol、Indisulam、AZD5438、SNS-032（BMS-387032）、Bryostatin-1、PD 0332991等 CDKIs 在肿瘤靶向性治疗中的研究作一综述。
세포주기시세포생명활동적기본과정，타공제착세포종정지기전향생장증식기。세포주기단백의뢰격매（Cdks）화세포주기단백（Cyclins）시정개세포주기조공궤제중적핵심분자。세포주기조공이상여세포암변밀절상관，90％이상적종류，우기시효질류화연조직육류중 Cdks 도유과도표체。진일보분석지출，Cdks 화 Cyclins 피작위치료종류적관건파점，타문수억제시능도치종류세포적사망，억제 Cdks 환능조체 Cyclins 전록。Ⅰ기림상연구제시，세포주기소단백격매억제제（CDKIs）유교고적안전성；Ⅱ기림상연구제시，CDKIs 연합세포독성화료약물작용종류세포유경호적전경，차 CDKIs 적사용제량화시간순서결정착기최가사용효과。본문천술료 Cdks 화 Cyclins재종류세포주기중적표체，대 Flavopiridol、Indisulam、AZD5438、SNS-032（BMS-387032）、Bryostatin-1、PD 0332991등 CDKIs 재종류파향성치료중적연구작일종술。
ABSTRACT:Cell cycle is the basic process of cell life activities.It controls the entry of stationary-phase cells into proliferative phase.Cyclin dependent kinases(Cdks)and cyclins play important roles in the regulatory mechanism of cell cycle.The dysregulation of cell cycle is closely related to the canceration.The Cdks is overexpressed in 90% of tumors,especially in glioma and soft tissue sarcoma.Cdks and cyclins are considered as the target of tumor therapy.Tumor cell death can be caused by the inhibition of both proteins.Furthermore,the transcription of cyclins can be inhibi-ted by Cdks.Phase Ⅰ clinical trial has shown that the cyclin-dependent kinase inhibitors(CDKIs) have higher security.Phase Ⅱ clinical trial has demonstrated that the combination CDKIs and cy-totoxic chemotherapy drugs has a better prospect and the dose and sequential order of usage of CDKIs are extremely important for their efficacy.This paper reviews the expression of Cdks and cyclins in tumor cell cycle and roles of flavopiridol,indisulam,AZD5438,SNS-032(BMS-387032), bryostatin-1,PD 0332991 and other CDKIs in target-guided tumor therapy.