Effect of Ad-p16 combined with CDDP or As₂O₃ on human bladder cancer cells

Abstract

To evaluate the therapeutic efficiency of combined use of p16-expressing adenovirus and chemotherapeutic agents CDDP or As₂O₃ on human bladder cancer cell line EJ, the human bladder cancer cell line EJ were transfected with adenovirus-mediated p16 gene (Ad-p16), with administration of cisplatin (CDDP) or arsenic trioxide (As₂O₃). The cell growth, morphological changes, cell cycle, apoptosis and molecular changes were measured using cell counting, reverse microscopy, flow cytometry, cloning formation, immunocytochemical assays andin vivo therapy experiments to evaluate the therapeutic efficacy of such combined regimen. Ad-p16 transfer and CDDP or As₂O₃ administration to EJ cells could exert substantially stronger therapeutic effects than the single agent treatment. Especially inin vivo experiments, combined administration of p16 and CDDP or As₂O₃ induced almost tumor diminish compared to the partial tumor diminish induced by single agent. Moreover, delivery of Ad-p16, or administration of minimal-dose CDDP or As₂O₃ or combined regimen could induce massive apoptosis of EJ cell. Cell cycle analysis demonstrated that administration of CDDP or As₂O₃ remarkably arrested EJ cell in G₁ prior to apoptotic cell death. When treated with combined regimen, cells were arrested in G₁ to a greater extent prior to apoptotic cell death. It is concluded that after introduction into EJ cell, Ad-p16 shows enhanced therapeutic efficacy for EJ cell when used in combination with CDDP or As₂O₃.

Keywords

cisplatin / arsenic trioxide / Ad-p16 / bladder cancer

References

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