title: The use of ATP bioluminescence assays in selecting a drug screen panel for chemosensitivity testing of uterine cancer cell lines.
abstract: The ATP bioluminescence assay has demonstrated a strong potential to become a clinical assay for chemosensitivity testing. Currently, chemotherapy of gynecologic cancers remains controversial and empirical. To optimize the patient's chance of survival and to justify related toxicities, the chemoregimen should be individualized and based on the patient's chemosensitivity profiles. This study was performed to identify a panel of active drugs against uterine cancer cell lines for possible use in future chemosensitivity testing. We used the ATP chemosensitivity assays to screen 12 common cytotoxic agents against six uterine cancer cell lines. Drug concentrations required for a 50% surviving fraction were defined as IC50s. When using an IC50 of 0.21 PPC (peak plasma concentration) as a cutoff value for sensitivity, the following 8 drugs were considered effective for uterine cancer cell lines: actinomycin D, Adriamycin, vinblastine, etoposide, 5-fluorouracil, methotrexate, cytosine arabinoside, and mitomycin-C. Meanwhile, 4 drugs, cisplatin, 4OH-Cytoxan, bleomycin, and Alkeran with mean IC50s of 2.1 +/- 0.7, 0.8 +/- 0.1, greater than 5.0, and 0.75 +/- 0.36 PPC, respectively, were considered inactive or partially active with higher IC50s than peak plasma concentrations. In conclusion, the above panel of promising drugs can be further tested in animal models or human cancer specimens for possible use in chemosensitivity testing of uterine cancer patients.
authors.affiliation: Department of Obstetrics & Gynecology, University of Miami School of Medicine, Florida 33101.
authors.forename: H N
authors.initials: HN
authors.lastname: Nguyen
authors.forename: B U
authors.initials: BU
authors.lastname: Sevin
authors.forename: H E
authors.initials: HE
authors.lastname: Averette
authors.forename: J
authors.initials: J
authors.lastname: Perras
authors.forename: D
authors.initials: D
authors.lastname: Donato
authors.forename: M
authors.initials: M
authors.lastname: Penalver
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000255:Adenosine Triphosphate / Q000032:analysis*; D000470:Alkaloids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D007700:Kinetics; D008163:Luminescent Measurements; D008558:Melphalan / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D007364:Intercalating Agents; C012358:4-hydroxycyclophosphamide; D016685:Mitomycin; D000255:Adenosine Triphosphate; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan