Journal article
Combined action of paclitaxel and cisplatin against wildtype and resistant human ovarian carcinoma cells
Cancer chemotherapy and pharmacology, Vol.40(6), pp.495-505
09/04/1997
DOI: 10.1007/s002800050693
PMID: 9332464
Abstract
Purpose: The combination of paclitaxel (PTX) and cisplatin (DDP) shows good clinical efficacy against ovarian cancer. In order to examine the potential cellular basis for this, and provide leads as to how to optimize the combination, we examined the role of sequence of exposure to PTX and DDP on cell growth in vitro. Methods: Four human ovarian carcinoma cell lines, A121, A2780/WT, A2780/DX5B and A2780/CP3, two human head and neck carcinoma cell lines, A253 and FaDu, and the human ileocecal carcinoma cell line, HCT-8, were treated with PTX + DDP with seven schedules: (A) 96 h exposure to PTX + DDP; (B) 24 h PTX alone, then 72 h PTX + DDP; (C) 4 h DDP alone, then 92 h PTX + DDP; (D) 24 h PTX alone, 4 h DDP alone, then 68 h drug-free; (E) 4 h DDP alone, 24 h PTX alone, then 68 h drug-free; (F) 3 h PTX alone, 1 h DDP alone, then 92 h drug-free; and (G) 1 h DDP alone, 3 h PTX alone, then 92 h drug-free. Each of 66 two-drug experiments included five plates (440 randomly treated wells per experiment). Cell growth was measured by the sulforhodamine B assay. The nature and the intensity of the drug interactions were assessed by fitting a seven-parameter model to data with weighted nonlinear regression, enabling the estimation of an interaction parameter, α, with its standard error. Results: Overall there was very little departure from Loewe additivity: 43 experiments showed Loewe additivity, 10 showed Loewe antagonism, and 13 showed slight Loewe synergy. In vitro Loewe synergy was rare, was small when present, and reproducible only for the A121 and HCT-8 cells exposed to schedule D (24 h PTX prior to 4 h DDP). Isobolographic analysis showed complex combined-action surfaces with regions of local Loewe synergy and antagonism. Conclusion: It appears unlikely that the good clinical efficacy of the combination is primarily caused by a synergistic interaction at the cellular level.
Details
- Title: Subtitle
- Combined action of paclitaxel and cisplatin against wildtype and resistant human ovarian carcinoma cells
- Creators
- Laurence M. Levasseur - Roswell Park Cancer InstituteWilliam R. Greco - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer InstituteHarry K. Slocum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.40(6), pp.495-505
- DOI
- 10.1007/s002800050693
- PMID
- 9332464
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Language
- English
- Date published
- 09/04/1997
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359775302771
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