Evidence that progesterone receptor antagonists may help in the treatment of a variety of cancers by locally suppressing natural killer cell activity.
OBJECTIVE
To propose a novel concept that progesterone receptor antagonists, e.g., mifepristone, may prove effective in treating a variety of cancers--even those not shown to be hormonally dependent or possessing progesterone receptors.


METHODS
Multiple human leukemia cell lines were evaluated for mRNA expression of an immunomodulatory protein called the progesterone-induced blocking factor (PIBF) that suppresses natural killer (NK) cell activity during normal pregnancy. Furthermore, we evaluated the effects of progesterone (P) and mifepristone in PIBF protein expression. Finally, the effect of mifepristone treatment of mice with advanced leukemia was evaluated.


RESULTS
All tumor cell lines evaluated were found to express mRNA for PIBF and some were found to even express the PIBF protein. The addition of P to the media increased the expression of PIBF and mifepristone downregulated its expression. Treatment of mice with spontaneous leukemia when they already had extensive disease seemed to increase the length and quality of their life.


CONCLUSIONS
These data and other experience with mice with lung cancer and some anecdotal human cancer experience suggest that various cancers may utilize similar mechanisms used by the fetus to escape NK cell surveillance. Mifepristone and other progesterone receptor antagonists may deserve a clinical trial in human cancer even where there is no knowledge of the presence of progesterone receptors.
Check
J H
JH
Sansoucie
L
L
Chern
J
J
Amadi
N
N
Srivastava
M
M
Larece
K
K
D000818:Animals; D045744:Cell Line, Tumor; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013491:Suppressor Factors, Immunologic
D006727:Hormone Antagonists; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D013491:Suppressor Factors, Immunologic; D015735:Mifepristone; D011374:Progesterone