端粒及其类似物在肿瘤靶向治疗中的研究进展

Research progress of telomere and its analogues in tumor targeted therapy

端粒与细胞凋亡、衰老及肿瘤的发生、发展有着密切联系,端粒长度及其结构的完整性在肿瘤细胞的无限增殖中具有重要作用。人端粒末端具有富含鸟嘌呤的串联结构(TTAGGG),其单链悬出末端回旋形成loop环维持端粒功能稳定,该序列在一定情况下能自发形成G-四链体(G4)。G4的形成会从结构上抑制端粒酶或者ALT延长端粒的作用从而具有抗肿瘤特性。与端粒同源的寡核苷酸(T-Oligo)入核后会引发肿瘤细胞的DNA损伤反应,通过激活ATM(毛细血管共济失调基因)通路,上调p53、p73、p95/Nbs1等下游因子,使肿瘤细胞发生衰老或凋亡。本文综述端粒及其类似物在肿瘤靶向治疗中的研究进展,为肿瘤临床治疗奠定基础。

Telomere is closely related to apoptosis,cellular senescence,tumorigenesis and development.Telomere length and its structural integrity play an important role in the infinite proliferation of tumor cells.The telomere end has a guanine-rich tandem structure(TTAGGG),and its single-stranded hanging end turns to form a loop to maintain telomere function,and the sequence spontaneously forms a G-quadruplex(G4)under certain conditions.The formation of G4 will inhibit telomerase structurally or the effect of ALT on extending telomeres,so as to have anti-tumor properties.Oligonucleotides(T-Oligo),homologous to telomeres,can cause DNA damage in tumor cells after entering the nucleus,and make tumors cells undergoing aging or apoptosis via activating the ataxia telangiectasia mutated(ATM)pathway to up-regulate downstream factors such as p53,p73 and p95/Nbs1.This review summarized the research progress of telomeres and their analogues in tumor targeted therapy,and lays a foundation for clinical treatment of tumors.