ABSTRACT

Autophagy induced in cancer cells during chemotherapy is classified into two types, which differ depending on the kind of cells or anticancer drugs. The first type of autophagy contributes to the death of cells treated with drugs. In contrast, the second type plays a crucial role in preventing anticancer drug-induced cell damages; the use of an autophagy inhibitor is considered effective in improving the efficacy of chemotherapy. Thus, it is important to determine which type of autophagy is induced during chemotherapy. Here, we showed that a novel inhibitor of RNA polymerase I, suppresses growth, induces cell cycle arrest and promotes apoptosis in leukemia cell lines. The number of apoptotic cells induced by co-treatment with CX-5461 and chloroquine, an autophagy inhibitor, increased compared with CX-5461 alone. Thus, the autophagy which may be induced by CX-5461 was the second type.

摘要

化疗期间在癌细胞中诱导的自噬可分为两种类型，这取决于细胞或抗癌药物的种类。第一种自噬会导致药物治疗的细胞死亡。相反，第二种在预防抗癌药诱导的细胞损伤中起着至关重要的作用。自噬抑制剂的使用被认为可以有效地改善化学疗法的功效。因此，重要的是确定在化学疗法期间诱导哪种自噬类型。在这里，我们显示了一种新型的RNA聚合酶抑制剂，可抑制白血病细胞的生长，诱导其细胞周期停滞并促进其凋亡。与单独的CX-5461相比，通过与CX-5461和自噬抑制剂氯喹共同处理诱导的凋亡细胞数量增加。从而，