Spitz F R, Nguyen D, Skibber J M, Cusack J, Roth J A, Cristiano R J
Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Anticancer Res. 1996 Nov-Dec;16(6B):3415-22.
The p53 tumor suppressor gene is altered in up to 70% of colorectal cancers.
We infected the colorectal cancer cell lines SW620 and KM12L4, in which p53 is mutated, with the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effects of adenovirus-mediated wild-type p53 gene transfer. Gene transduction was measured by cytochemical staining of cells infected with the Ad5/CMV/beta-gal virus and expression of the wildtype p53 protein in these cells was demonstrated by immunoblotting.
Significant suppression of in vitro cell proliferation and induction of apoptosis (as measured by TUNEL assay labeling) were observed following Ad5/CMV/p53 infection. More importantly, similar effects were observed in vivo in an established nude mouse subcutaneous tumor model; significant suppression of tumor growth (60%-70%) and induction of apoptosis were observed following intratumoral injections of Ad5/CMV/p53.
This form of therapy may provide a novel approach to colorectal cancer.
高达70%的结直肠癌中p53肿瘤抑制基因发生改变。
我们用复制缺陷型腺病毒Ad5/CMV/p53感染p53基因发生突变的结直肠癌细胞系SW620和KM12L4，以评估腺病毒介导的野生型p53基因转移的效果。通过对感染Ad5/CMV/β-半乳糖苷酶病毒的细胞进行细胞化学染色来检测基因转导，并通过免疫印迹法证明这些细胞中野生型p53蛋白的表达。
Ad5/CMV/p53感染后观察到体外细胞增殖受到显著抑制以及细胞凋亡的诱导（通过TUNEL检测标记法测定）。更重要的是，在已建立的裸鼠皮下肿瘤模型中在体内观察到了类似的效果；瘤内注射Ad5/CMV/p53后观察到肿瘤生长受到显著抑制（60%-70%）以及细胞凋亡的诱导。
这种治疗形式可能为结直肠癌提供一种新的治疗方法。
