n-3 polyunsaturated fatty acids decrease mucosal/epidermal reactions and enhance antitumour effect of ionising radiation with inhibition of tumour angiogenesis.
The purpose of this study was to evaluate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on normal tissue (lip mucosa) and tumour growth when combined with ionising radiation. The oral region (snout) of C57 black mice was irradiated with 16.5 Gy and n-3 PUFAs (100 microl) were injected intravenously for 2 weeks. After exposure to irradiation, the degree and duration of the acute reactions decreased significantly when mice were treated with n-3 PUFAs as compared to the control group. Interestingly, the range of the reactions in the n-3 PUFAs-treated group compared favourably to the group receiving amifostine (27.5 mg/kg i.v.). the effect of n-3 PUFAs was further evaluated in HEP-2 human carcinoma xenograft transplanted in nude mice. An inhibition of tumour growth was observed when mice were treated with n-3 PUFAs alone and this effect was maximal when combined with irradiation. Similar results were obtained using eicosapentaenoic acid. The effect of n-3 PUFAs was associated with inhibition of angiogenesis and tumour proliferation, and significantly decreased expression of cyclooxygenase-2. In conclusion, n-3 PUFAs administration decrease mucosal response, while moderately enhancing the antitumour effect of irradiation. The magnitude of the differential effect suggests that n-3 PUFAs need to be further investigated in the clinic.
Wen
B
B
Laboratoire UPRES EA No. 27-10 Radiosensibilité des tumeurs et tissus sains, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94805 Villejuif Cédex, France.
Deutsch
E
E
Opolon
P
P
Auperin
A
A
Frascogna
V
V
Connault
E
E
Bourhis
J
J
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000737:chemistry; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000528:radiation effects; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils; D006258:Head and Neck Neoplasms / Q000473:pathology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009092:Mucous Membrane / Q000187:drug effects / Q000528:radiation effects; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014280:Triglycerides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000637:transplantation
D017931:DNA Primers; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D000960:Hypolipidemic Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D014280:Triglycerides; C077446:Pikasol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases