OBJECTIVETo explore the effects of adenovirus delivered tissue inhibitor of metalloproteinases-3 (Ad-TIMP-3) on the biological behaviors of cervical cancer cell lines and to evaluate its potential application in cervical cancer gene therapy.

METHODSWe transferred Ad-TIMP-3 into cervical cancer cells. The TIMP-3 mRNA expression was assessed by RT-PCR, and the TIMP-3 and p53 protein expressions were assessed with Western blot. The apoptotic changes of cells were illustrated with morphology and DAPI staining. The viability of cells was determined with MTT assay. The abilities of in vitro invasion and adhesion were evaluated by the invasion and adhesion assays respectively.

RESULTSAfter infection, the TIMP-3 mRNA and protein were significantly upregulated in a time-dependent manner. Overexpression of TIMP-3 markedly increased p53 protein level in spite of the backgrounds of p53 gene in cells. Ad-TIMP-3 infection induced massive apoptosis of cervical cancer cells with a marked bystander effect. The abilities of in vitro invasion and adhesion were inhibited significantly (P < 0.01). The cytotoxicity of Ad-TIMP-3 was significantly stronger than that of Ad-p53 (P < 0.05, P < 0.01).

CONCLUSIONSAd-TIMP-3 infection has cytotoxic effects on cervical cancer cells and can inhibit the expressions of these malignant phenotypes. Ad-TIMP-3 may be a potentially useful agent for cervical cancer gene therapy.