Cyclooxygenase inhibitors are potent sensitizers of prostate tumours to hyperthermia and radiation.
It has previously been demonstrated that hyperthermia can activate prostaglandin synthesis and that prostaglandins are protective against hyperthermia. This study examined the use of inhibitors of prostaglandin synthesis on the response of prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit prostaglandin production, were effective hyperthermia sensitizers and augmented growth delay of DU-145 and PC-3 prostate tumours to combined radiation and hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01) inhibition of hyperthemia-induced serum prostaglandin E2. These findings indicate that NSAID may have both sensitizing effects on prostate tumour growth and may function by inhibiting prostaglandin synthesis.
Asea
A
A
Department of Radiation Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Mallick
R
R
Lechpammer
S
S
Ara
G
G
Teicher
B A
BA
Fiorentino
S
S
Stevenson
M A
MA
Calderwood
S K
SK
D000818:Animals; D003131:Combined Modality Therapy; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D006979:Hyperthermia, Induced; D007052:Ibuprofen / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013467:Sulindac / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D011838:Radiation-Sensitizing Agents; D013467:Sulindac; D007975:Leukotriene B4; D015232:Dinoprostone; D007052:Ibuprofen