Effect of Ad-TIMP3 on biologic behavior of choriocarcinoma cells in vitro.
OBJECTIVE
To investigate the effect of adenovirus delivered tissue inhibitor of metalloproteinases-3 (Ad-TIMP3) on the biologic behavior of choriocarcinoma cells in vitro and to evaluate its potential application in choriocarcinoma gene therapy.


METHODS
An adenovirus expressing TIMP3 (Ad-TIMP3) was transferred into choriocarcinoma cells jeg-3 and bewo. The mRNA and protein expression of TIMP3 were detected by reverse transcriptase polymerase chain reaction and Western blotting. MTT assays performed to study the growth inhibitory and proapoptotic effects of TIMP3 in vitro were examined by FACS and DAPI staining. The effect of Ad-TIMP3 on the abilities of adhesion and invasion were evaluated by adhesion and invasion assay, respectively.


RESULTS
TIMP3 was expressed less in jeg-3 and bewo than in HEK293 cells. TIMP3 was up-regulated in both cells as a response to Ad-TIMP3 treatment. Ad-TIMP3 significantly inhibited the growth of jeg-3 and bewo cells by inducing the apoptosis of jeg-3 and bewo. The abilities of adhesion and invasion were inhibited significantly by Ad-TIMP3 as well. Furthermore, TIMP3 exerted a cytotoxic bystander effect on adjacent uninfected cells.


CONCLUSIONS
In addition to its role in inhibiting tumor adhesion and invasion, TIMP3 induced the apoptosis and inhibited the growth of jeg-3 and bewo choriocarcinoma cells. Furthermore, TIMP3 exerted a cytotoxic bystander effect on adjacent uninfected cells. Ad-TIMP3 may be potentially useful in treating choriocarcinoma.
Chen
Yan
Y
Department of Obstetrics and Gynecology, and State Key Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, People's Republic of China.
Qian
Haili
H
Zhang
Ying
Y
Ma
Yan
Y
Lin
Chen
C
Xiang
Yang
Y
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D009361:Neoplasm Invasiveness; D011247:Pregnancy; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
D019717:Tissue Inhibitor of Metalloproteinase-3