Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B, Williams J
Johns Hopkins Oncology Center, Program in Human Genetics, Baltimore, Maryland 21231, USA.
Nat Med. 1997 Sep;3(9):1034-6. doi: 10.1038/nm0997-1034.
In response to anticancer therapeutics, human colon cancer cells growing in vitro either enter into a stable arrest or die, depending on the integrity of their cell-cycle checkpoints. To test whether altered checkpoints can modulate sensitivity to treatment in vivo, xenografts were established from isogenic lines differing only in their p21 checkpoint status. Although all tumors with intact checkpoint function underwent regrowth after treatment with gamma-radiation, a significant fraction of checkpoint-deficient tumors were completely cured. This difference in sensitivity was not detected by the clonogenic survival assay, because both arrest and death preclude outgrowth of colonies. These results demonstrate that checkpoint status affects sensitivity to anticancer treatments in vivo, and these findings have important implications for identifying and testing new therapeutic compounds.
针对抗癌疗法，体外培养的人结肠癌细胞要么进入稳定停滞状态，要么死亡，这取决于其细胞周期检查点的完整性。为了测试改变的检查点是否能在体内调节对治疗的敏感性，从仅p21检查点状态不同的同基因系建立了异种移植瘤。尽管所有具有完整检查点功能的肿瘤在接受γ射线治疗后都出现了再生长，但相当一部分检查点缺陷的肿瘤被完全治愈。克隆形成存活试验未检测到这种敏感性差异，因为停滞和死亡都会阻止集落生长。这些结果表明，检查点状态会影响体内对抗癌治疗的敏感性，这些发现对于鉴定和测试新的治疗化合物具有重要意义。
