细胞周期蛋白依赖激酶抑制剂与女性恶性肿瘤的研究进展

Study advances in Cyclin-dependent kinase inhibitors and female malignant tumors

细胞周期紊乱可导致细胞异常增殖,而细胞异常增殖与肿瘤的发生密切相关。正常情况下,细胞周期的内源性调控主要是通过磷酸化和去磷酸化为基础的细胞周期蛋白(Cyclin)-细胞周期蛋白依赖激酶(CDK)-细胞周期蛋白依赖激酶抑制剂(CKI)途径实现的。其中,CKI如P16、P21、P27对细胞周期起负调控作用,当细胞发生异常增殖时,其直接与CDK或CDK-Cyclin复合体结合,抑制CDK活性,使细胞周期停滞,从而避免肿瘤发生。研究发现,多种信号通路可调控CKI的表达,当CKI表达异常时可导致多种女性恶性肿瘤的发生,甚至严重影响肿瘤分期和患者预后。因此,通过研究不同信号通路下不同CKI的表达水平,将为今后女性恶性肿瘤的临床治疗提供新的理论基础。

The cell cycle disorders can lead to abnormal cell proliferation which is closely related to the occurrence of tumors.Under the normal circumstances,the endogenous regulation of cell cycle is mainly achieved by cyclin-cyclin dependent kinase(CDK)-cyclin dependent kinase inhibitor(CKI)pathway with the phosphorylation and dephosphorylation as the basis.Among them,CKI such as P16,P21 and P27 plays a negative regulating effect on cell cycle.When abnormal cell proliferation occurs,CKI binds directly to CDK or CDK-Cyclin complex,inhibits CDK activity,blocks the cell cycle,thus avoids the tumorigenesis.The study finds that multiple signal pathways can regulate the CKI expression.When CKI is abnormally expressed,it can lead to the occurrence of multiple female malignant tumors,even seriously affects the tumor staging and patient′s prognosis.Therefore investigating the expression level of different CKI under different signal pathways provides a new theoretical basis for the clinical treatment of female malignant tumor in the future.