1.Restoration of Wild-Type p53 by Adenovirus-Mediated Gene Transfer May Enhance the Therapeutic Efficacy of Chemotherapy in Human Ovarian Cancer Cells.
Tae Eung KIM ; Yong Wook KIM ; Heung Ki KIM ; Duck Yeong RO ; Jin Woo KIM ; Jae Keun JUNG ; Dirk G KIEBACK ; Sung Eun NAMKOONG
Korean Journal of Gynecologic Oncology and Colposcopy 2001;12(1):23-30
OBJECTIVE: In an effort to develop a more effective therapeutic strategy for ovarian cancer, we examined whether the restoration of the wild-type p53 gene can enhance the therapeutic effect of chemotherapy. METHODS: In this study, Ov-ca-2774 cells, which are known to have p53 point mutation and cisplatin-resistance, were selected and currently used chemotherapeutic agents including cisplatin, carboplatin, paclitaxel, etoposide, topotecan, and doxorubicin were added concurrently or sequentially with adenovirus-mediated p53 gene transfer (Ad5CMV-p53). RESULTS: Transfer of the wild-type p53 cDNA gene into Ov-ca-2774 cells showed 55% cell killing in vitro at a multiplicity of infection (MOI) of 40. Although the combination of carboplatin or paclitaxel followed by p53 gene transfer with an interval of 48 h manifested no enhanced cell killing compared with cells infected with Ad5CMV-p53 alone, the other combinations of chemotherapeutic agents and p53 gene transfer resulted in 15% to 37% further cell killing (P<0.05). Furthermore, p53 gene transfer followed by doxorubicin with an interval of 24 h and concurrent combination of etoposide with p53 gene transfer showed significant difference in cell killing in contrast to the other combination strategies in the respective chemotherapeutic agent exposure groups (P<0.05). CONCLUSION: Our data demonstrated that combination of p53 gene transfer and chemotherapeutic agents had higher cell killing than either of these two modality alone.
Carboplatin
;
Cisplatin
;
DNA, Complementary
;
Doxorubicin
;
Drug Therapy*
;
Etoposide
;
Genes, p53
;
Homicide
;
Humans*
;
Ovarian Neoplasms*
;
Paclitaxel
;
Point Mutation
;
Topotecan