Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.
Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.
复制标题
反义DNA抑制c-Ha-ras癌基因诱导的裸鼠肿瘤生长。
作者：
Gary D. Gray;Olga M. Hernandez;Denise Hebel;Malcolm Root;Julio M. Pow;Eric Wickstrom
反义DNA已显示出针对特定癌基因转录物并抑制其在细胞中表达的能力，但持续治疗在多大程度上可以抑制致癌产物的总水平并改变体内的肿瘤发生仍有待确定。本研究以人膀胱癌T24细胞中活化的c-Ha-ras癌基因转化的NIH-3T3细胞为研究对象，用c-Ha-ras RNA转录本5‘侧翼区靶点的反义DNA十五聚体处理NIH-3T3细胞，连续3天。在反义DNA处理后，一部分细胞裂解以测量RAS p21，而其余细胞通过注射S.C.评估成瘤性。以5×10(5)细胞/只的剂量注入裸鼠体内。在3天的治疗中，抗c-Ha-ras DNA使ras p21细胞水平下降了90%以上，而非特异性对照DNA使p21水平下降了约20%。经抗c-Ha-ras DNA处理的小鼠肿瘤生长在治疗结束后14天内显着降低，而非特异性对照DNA则无明显作用。这些对肿瘤生长的影响在两种不同品系的裸鼠身上以及在雄性和雌性裸鼠身上都很明显。结果表明，反义c-Ha-ras DNA诱导的ras p21表达水平显著降低，导致转化表型逆转，这是反义DNA治疗后肿瘤发生持续抑制的原因。
Antisense DNA has shown an ability to target specific oncogene transcripts and inhibit their expression in cells, but the degree to which sustained treatment can suppress total levels of an oncogenic product and alter tumorigenesis in vivo remains to be determined. In this study, NIH-3T3 cells transformed by the activated c-Ha-ras oncogene from T24 human bladder cancer cells were treated for 3 consecutive days in vitro with an antisense DNA pentadecamer complementary to a target in the 5'-flanking region of the c-Ha-ras RNA transcript. Following antisense DNA treatment, a portion of the cells was lysed for measurement of RAS p21 while the remaining cells were evaluated for tumorigeneity by injection s.c. into athymic nude mice at a dose of 5 x 10(5) cells/mouse. The 3 days of treatment with the anti-c-Ha-ras DNA reduced RAS p21 cellular levels by more than 90% while a nonspecific control DNA reduced p21 levels by approximately 20%. Tumor growth of cells treated with anti-c-Ha-ras DNA was significantly reduced for up to 14 days following the end of treatment and implantation into the mice whereas the nonspecific control DNA had no significant effect. These effects on tumor growth were evident in two different strains of nude mice and in both males and females. It is suggested that the pronounced decrease in RAS p21 levels produced by anti-c-Ha-ras DNA resulted in a reversal of the transformed phenotype, and it is this reversal which accounts for the prolonged inhibition of tumorigenesis following antisense DNA treatment.
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影响因子：
11.2
作者：
Joyce Bos
通讯作者：
Joyce Bos
T24 转化的 NIH3T3 细胞中反义寡脱氧核苷酸抑制 c-Ha-ras p21 表达和病灶形成的靶点依赖性。
DOI：
--
发表时间：
1990
期刊：
Oncogene research
影响因子：
--
作者：
Daaka,Y;Wickstrom,E
通讯作者：
Wickstrom,E
ras 对保守序列元件的转录激活需要不同于 c-fos 或 c-jun 的核因子。
DOI：
10.1073/pnas.87.10.3866
发表时间：
1990
影响因子：
11.1
作者：
Owen,RD;Ostrowski,MC
通讯作者：
Ostrowski,MC
DOI：
10.1073/pnas.85.14.5011
发表时间：
1988-07-01
影响因子：
11.1
作者：
WALDER, RY;WALDER, JA
通讯作者：
WALDER, JA
影响因子：
56.9
作者：
SLAMON, DJ;GODOLPHIN, W;PRESS, MF
通讯作者：
PRESS, MF