Giovannetti E, Backus H H J, Wouters D, Peters G J
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):740-5. doi: 10.1080/15257770802145512.
The role of p53 in altering TS expression and chemosensitivity was studied in colorectal cancer cells with wildtype, mutated, or functionally inactive p53. Cytotoxicity of TS inhibitors was studied by MTT, while PCR, Western blot, and activity assays assessed whether p53 status influenced TS expression. Lovo-175X2 cells showed increased resistance to TS inhibitors and significantly greater than wildtype expression and activity of TS. In contrast, Lovo-273X17 and Lovo-li were more sensitive to TS inhibitors and had reduced TS expression, due either to reduced TS mRNA or altered regulation of TS activity. Thus, functional inactivity and mutations of p53 differentially affect TS, potentially influencing response to TS inhibitor-based treatment.
在具有野生型、突变型或功能失活型p53的结肠癌细胞中研究了p53在改变胸苷酸合成酶（TS）表达和化疗敏感性方面的作用。通过MTT研究TS抑制剂的细胞毒性，而通过聚合酶链反应（PCR）、蛋白质免疫印迹法（Western blot）和活性测定评估p53状态是否影响TS表达。洛沃-175X2细胞对TS抑制剂的耐药性增加，且TS的表达和活性显著高于野生型。相反，洛沃-273X17和洛沃-li对TS抑制剂更敏感，且TS表达降低，这要么是由于TS信使核糖核酸（mRNA）减少，要么是由于TS活性的调节改变所致。因此，p53的功能失活和突变对TS有不同影响，可能影响基于TS抑制剂的治疗反应。
