Somatostatin analogue octreotide modulates metabolism and effects of 5-fluorouracil and 5-fluorouridine in human colon cancer spheroids.
To examine if preferential retention of somatostatin analogues observed in some tumors might be used for modulation of effects of cancer drugs by co-treatment with long acting somatostatin analogues, the effects of somatostatin analogue octreotide on the kinetics of 5-fluorouracil (FUra) and 5-fluorouridine (FUrd) metabolism were studied by 19F NMR spectroscopy in multicell tumor spheroids comprised of human colon HT-29 adenocarcinoma cells. Octreotide stimulated the rate of formation of fluorouridinephosphates in FUra-treated cells, but inhibited this rate in FUrd-treated cells. Other elements of fluoropyrimidine metabolism were also altered by co-incubation with octreotide. A flow cytometric analysis indicated that FUra and FUrd arrested cells in the S phase, but co-treatment with octreotide almost eliminated the S-phase cells and induced the appearance of DNA fragments. These observations raise the possibility that somatostatin analogues can be used for specific modulation of fluoropyrimidine effects in tumors bearing somatostatin receptors.
Chen
T B
TB
Department of Oncology, Mayo Clinic, Rochester, MN 55905.
Huzak
M
M
Macura
S
S
Vuk-Pavlović
S
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D005461:Fluorine; D005472:Fluorouracil / Q000378:metabolism* / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015282:Octreotide / Q000494:pharmacology*; D012335:RNA, Ribosomal / Q000037:antagonists & inhibitors; D017481:Receptors, Somatostatin / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014529:Uridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D004273:DNA, Neoplasm; D012335:RNA, Ribosomal; D017481:Receptors, Somatostatin; D005461:Fluorine; C001943:5-fluorouridine; D015282:Octreotide; D005472:Fluorouracil; D014529:Uridine