Naruse I, Heike Y, Hama S, Mori M, Saijo N
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Anticancer Res. 1998 Nov-Dec;18(6A):4275-82.
In this study, we discussed the effects of treatment with recombinant adenovirus expressing p16 (AX-p16) on cell growth and cell death. Ax-p16 at 10 m.o.i. groups showed growth inhibition 3 days after gene transfection, but the cells regrew and did not undergo cell death. On the other hand, Ax-p16 at 300 m.o.i. groups showed complete cell growth inhibition leading to cell death which was apparent 7 days after p16 gene transfection. In the high m.o.i. Ax-mock groups, cell death was marked just after infection, but had diminished by 7 days after infection. Downregulation of pRB was detected only in Ax-p16 at 300 m.o.i. groups. These data suggest that a) high m.o.i. condition of Ax-p16 gives therapeutic benefits due to the combined effects of adenovirus and high expression of p16; and b) the cell killing mechanism of the p16 transgene is different from that of high m.o.i. adenoviral infection.
在本研究中，我们探讨了表达p16的重组腺病毒（AX-p16）处理对细胞生长和细胞死亡的影响。基因转染3天后，感染复数（m.o.i.）为10的Ax-p16组显示出生长抑制，但细胞重新生长且未发生细胞死亡。另一方面，感染复数为300的Ax-p16组显示出完全的细胞生长抑制并导致细胞死亡，这在p16基因转染7天后很明显。在高感染复数的Ax-空载体组中，细胞死亡在感染后立即明显，但在感染7天后有所减轻。仅在感染复数为300的Ax-p16组中检测到pRB的下调。这些数据表明：a）由于腺病毒和p16的高表达的联合作用，高感染复数的Ax-p16条件具有治疗益处；b）p16转基因的细胞杀伤机制与高感染复数腺病毒感染的机制不同。
