Combination analyses of anti-cancer drugs on human neuroendocrine tumor cell lines.
OBJECTIVE
There is a large need for better pharmacological treatment of neuroendocrine tumors. The aim of this study was to investigate and quantify the cytotoxic potentiating effects resulting from a combination of five substances, NSC 95397, emetine, CGP-74514A hydrochloride, Brefeldin A and sanguinarine chloride, chosen from a previous screening of 1,280 pharmacologically active agents on neuroendocrine tumor cells, with standard cytotoxic agents currently used in the treatment of neuroendocrine tumors.


METHODS
The human pancreatic carcinoid cell line BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were used. Combinations between doxorubicin, etoposide, oxaliplatin, docetaxel, and each one of the five agents were studied and simultaneous exposures were explored using the median-effect method.


RESULTS
Most of the combinations of NSC-95397 and emetine with doxorubicin, etoposide, docetaxel, and oxaliplatin showed synergism, and their remaining combinations were additive. Almost all of the CGP-74514A hydrochloride interactions were additive, while brefeldin A and sanguinarine displayed less synergy but more additive and antagonistic interactions in combination with the standard drugs.


CONCLUSIONS
The synergistic and additive interactions make NSC-95397, emetine, and CGP-74514A hydrochloride potential candidates for incorporation into combination chemotherapy regimens and these drugs might be the suitable candidates for further clinical studies in patients with bronchial carcinoids and pancreatic endocrine tumors.
Larsson
Dhana E
DE
Department of Endocrine Oncology, Faculty of Medicine, University of Uppsala, University Hospital, 751 85 Uppsala, Sweden. dhana.larsson@medsci.uu.se
Hassan
Sadia
S
Larsson
Rolf
R
Oberg
Kjell
K
Granberg
Dan
D
D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001984:Bronchial Neoplasms / Q000188:drug therapy / Q000473:pathology; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004640:Emetine / Q000008:administration & dosage; D006801:Humans; D009285:Naphthoquinones / Q000008:administration & dosage; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology
C451261:2,3-bis(2-hydroxyethylsulfanyl)-(1,4)naphthoquinone; C469937:N(2)-(2-aminocyclohexyl)-N(6)-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine; D009285:Naphthoquinones; D015075:2-Aminopurine; D004640:Emetine