PHA-767491抑制多种肿瘤细胞生长

Cdc7激酶抑制剂PHA-767491是最新发现的一类抗肿瘤新药.本实验利用不同浓度的PHA-767491对肿瘤细胞进行抑制研究.实验结果显示,PHA-767491对肿瘤细胞有很强的生长抑制作用,且抑制效果随着药物浓度或时间的增加而增强;通过和化疗药物5-氟尿嘧啶对比发现,PHA-767491只需较低剂量就能发挥出抑制肿瘤的作用,且疗效远高于5-氟尿嘧啶.研究进一步还发现,PHA-767491可通过促使PARP和casepase3蛋白的剪切诱导肿瘤细胞凋亡,同时PHA-767491还可以引起肿瘤细胞自噬.综上研究表明,PHA-767491可以通过诱导细胞凋亡和引起细胞自噬作用对多种肿瘤细胞有较好的治疗效果,而对正常细胞毒性很低.因此该实验研究为今后抗肿瘤新药PHA-767491的进一步应用于癌症的临床治疗提供了重要的实验依据.

PHA-767491 Inhibits Growth of Tumor Cells in Culture

Cdc7 kinase inhibitor PHA-767491 is a novel antitumor agent. This study aims to examine the antitumor activity of PHA-767491 against tumor cells and search for its molecular mechanism. Here we demonstrated that PHA-767491 played a critical role in the suppression of the proliferation of tumor cells in a concentration-and time-dependent manner. Compared with conventional chemotherapeutic drug 5-fluorouracil (5-FU), PHA-767491 showed a stronger antitumor effect at lower doses. In addition, we found that PHA-767491 induced remarkable apoptosis, evidenced by the cleavage of PARP and caspase 3, and autophagy also be observed in PHA-767491-treated tumor cells. We reported for the first time that PHA-767491 induced tumor cell death via apoptosis and autophagy, and appeared to be less cytotoxic for normal cell. These results suggest that Cdc7 kinase inhibitor PHA-767491 could be a new strategy for the development of anticancer therapeutics.