Restoration of Wild-Type p53 by Adenovirus-Mediated Gene Transfer May Enhance the Therapeutic Efficacy of Chemotherapy in Human Ovarian Cancer Cells.
- Author:
Tae Eung KIM
;
Yong Wook KIM
;
Heung Ki KIM
;
Duck Yeong RO
;
Jin Woo KIM
;
Jae Keun JUNG
;
Dirk G KIEBACK
;
Sung Eun NAMKOONG
- Publication Type:In Vitro ; Original Article
- Keywords:
Wild-type p53;
Adenoviral vector;
Chemotherapy;
Ovarian cancer
- MeSH:
Carboplatin;
Cisplatin;
DNA, Complementary;
Doxorubicin;
Drug Therapy*;
Etoposide;
Genes, p53;
Homicide;
Humans*;
Ovarian Neoplasms*;
Paclitaxel;
Point Mutation;
Topotecan
- From:Korean Journal of Gynecologic Oncology and Colposcopy
2001;12(1):23-30
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
