[Experimental study on combination of Ad-p53 with CDDP or As(2)O(3) in human lung adenocarcinoma cell line GLC-82]

Abstract

Objective: To evaluate the therapeutic efficiency of combining p53-expressing adenovirus with chemotherapy agents on GLC-82 human lung adenocarcinoma cells.

Methods: Human lung adenocarcinoma cell line GLC-82 was transfected with adenovirus-mediated p53 gene (Ad-p53) combining with administration of either kind of chemotherapeutic agents-cisplatin (CDDP) and arsenic trioxide (As(2)O(3)). The cell growth, morphological changes, cell cycle, apoptosis and molecular changes were measured using cell counting, reversmicroscope, flow cytometry, TUNEL, RT-PC, immunocytochemical assays, and in vivo therapy experiments to evaluate the therapeutic efficiency of such combined regimen.

Results: Ad-p53 transfer and CDDP (or As(2)O(3)) administration to GLC-82 cells could exertubstantially stronger therapeutic effects than the single agent treatment. Especially in in vivo experiments, combined administration of Ad-p53 and CDDP induced almost complete tumor remission (89.0%) compared to the partial tumor remission induced by single agent (43.9% or 57.3%). Moreover, delivery of Ad-p53, or administration of minimal-dose CDDP or As(2)O(3) or combined regimen could induce massive apoptosis of GLC-82 cells. Cell cycle analysis demonstrated that administration of CDDP or As(2)O(3) remarkably arrested GLC-82 cells in G(2)/M prior to apoptotic cell death. When treated with combined regimen, cells were arrested in G(2)/M to a greater extent prior to apoptotic cell death.

Conclusion: After introduced into GLC-82 cells, Ad-p53 shows enhanced therapeutic efficiency for GLC-82 cells when combined with CDDP or As(2)O(3).