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


CONCLUSIONS
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).
Xu
M
M
National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021 China.
Lin
C
C
Liang
X
X
D000230:Adenocarcinoma / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D015316:Genetic Therapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D010087:Oxides / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods; D019737:Transplants; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D001152:Arsenicals; D010087:Oxides; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D000077237:Arsenic Trioxide