ADENOVIRUS-MEDIATED GENE-TRANSFER OF WILD-TYPE P53 RESULTS IN MELANOMA CELL APOPTOSIS IN-VITRO AND IN-VIVO

被引：55

作者：

CIRIELLI, C

RICCIONI, T

YANG, CL

PILI, R

GLOE, T

CHANG, J

INYAKU, K

PASSANITI, A

CAPOGROSSI, MC

机构：

[1] NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,GENE THERAPY UNIT,BALTIMORE,MD 21224

[2] NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224

[3] IST DERMOPAT IMMACOLATA,PATOL VASC LAB,ROME,ITALY

来源：

INTERNATIONAL JOURNAL OF CANCER | 1995年 / 63卷 / 05期

关键词：

D O I：

10.1002/ijc.2910630512

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gene transfer techniques may provide efficient treatment for a variety of malignant neoplasms. A replication-deficient adenovirus (Ad) vector which carries the cDNA for wild-type p53 (AdCMV.p53) was tested for its in vitro and in vivo effects on the growth of murine melanoma cell line B16-G3.26 and human melanoma cell line SK-MEL-24. The growth of B16-G3.26 cells infected with AdCMV.p53 was inhibited when compared to the uninfected cells or cells infected with the control vector AdCMV.NLS beta gal. Similarly, the growth of SK-MEL-24 cells infected with AdCMV.p53 was also below that of AdCMV.NLS beta gal-infected and uninfected controls. DNA laddering using agarose gel electrophoresis and in site labeling of DNA fragmentation (TUNEL) showed that AdCMV.p53-infected murine and human melanoma cells underwent apoptosis. Nude mice injected s.c. either with B16-G3.26 cells or with SK-MEL-24 cells developed localized tumors. These tumors were subsequently infiltrated with either AdCMV.p53, AdCMV.NLS beta gal or saline alone. One week after infection, B16-G3.26 tumors exposed to AdCMV.p53 were 2.5 times smaller than control tumors and exhibited DNA fragmentation. A similar growth-inhibitory effect of AdCMV.p53 was observed with SK-MEL-24 tumors. Thus, Ad-mediated wildtype p53 overexpression resulted in melanoma cell apoptosis and inhibition of melanoma growth in vitro and in vivo. These gene therapy approaches may be useful in targeting rapidly growing, malignant melanomas in a clinical setting. (C) 1995 Wiley-Liss, Inc.

引用

页码：673 / 679

页数：7

共 32 条

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