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端粒酶的激活与肿瘤的发生、发展密切相关。尽管端粒酶在癌变过程中作用的分子机制尚未完全阐明,但大量实验证实端粒酶是一个理想的肿瘤治疗靶点。近年来人们尝试了许多方法抑制肿瘤细胞端粒酶活性,所产生的肮肿瘤作用并不完全一致。抑制肿瘤细胞端粒酶活性诱导细胞周期阻滞和(或)凋亡主要表现为两种形式即迟发型和即发型。此外,端粒酶活性抑制可以增加肿瘤细胞对化疗药物的敏感性。阐明端粒戴帽状态及端粒酶作用分子机制,建立针对端粒酶的高通量药物筛选法以及应用人癌动物移植模型进行体内药物抗瘤活性评价是端粒酶抑制剂开发中的三大方面。
Telomerase activation is closely related to tumorigenesis and development. Although the molecular mechanism of the role of telomerase in carcinogenesis has not yet been fully elucidated, a large number of experiments confirm that telomerase is an ideal target for tumor therapy. In recent years, many attempts have been made to inhibit the telomerase activity of tumor cells and the resulting tumorigenic effect is not exactly the same. Inhibition of telomerase activity in tumor cells induces cell cycle arrest and / or apoptosis mainly in two forms, delayed type and immediate type. In addition, inhibition of telomerase activity can increase the sensitivity of tumor cells to chemotherapeutic drugs. To elucidate the molecular mechanism of telomere wearing and telomerase, to establish a high-throughput drug screening method for telomerase and to evaluate the anti-tumor activity of the drug in vivo using the human cancer animal transplantation model are three Big deal