Enhanced polyadenosine diphosphate-ribosylation in gonadotropin-releasing hormone agonist-treated uterine leiomyoma.
This study aimed to examine the activation of poly(ADP-ribose) polymerase (PARP) and the accumulation of its end product, poly(ADP-ribose) (PAR), in uterine leiomyoma specimens obtained from 25 patients receiving Leuplin depot [leuprorelin acetate, depot (LA)] treatment and 46 control patients and explore their correlation with tumor shrinkage and degeneration caused by the therapy. Immunoblotting analysis showed that specimens from LA-treated patients had higher PARP expression. The numbers of both PARP- and PAR-immunolabeled cells were higher in leiomyoma with LA treatment. This was correlated with the clinical response of LA therapy that LA induced more leiomyoma degeneration. The analysis of power Doppler sonography indicated a progressive decrease in blood supply to tumor following LA treatment. In vitro experiments using primarily cultured leiomyoma cells exhibited that the deprivation of serum or ovarian hormones or LA directly failed to induce PARP and PAR production. Our results suggested that reduced blood flow and subsequent ischemic damages in leiomyoma could be responsible for PARP overexpression and PAR accumulation, clinical response, and tumor degeneration caused by LA treatment.
Huang
Soon-Cen
SC
Department of Obstetrics and Gynecology, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
Tang
Ming-Jer
MJ
Cheng
Ya-Min
YM
Hsu
Keng-Fu
KF
Ho
Chung-Liang
CL
Chou
Cheng-Yang
CY
D016587:Antimutagenic Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007889:Leiomyoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016729:Leuprolide / Q000494:pharmacology / Q000627:therapeutic use; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology; D018615:Ultrasonography, Doppler, Color; D015854:Up-Regulation / Q000187:drug effects; D014594:Uterine Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
D016587:Antimutagenic Agents; D018931:Antineoplastic Agents, Hormonal; D012739:Gonadal Steroid Hormones; D011064:Poly Adenosine Diphosphate Ribose; D007987:Gonadotropin-Releasing Hormone; D003035:Cobalt; D011065:Poly(ADP-ribose) Polymerases; D016729:Leuprolide; C018021:cobaltous chloride