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.

STUDY DESIGN

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.

CONCLUSION

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.