The Akt and ERK activation by platinum-based chemotherapy in ovarian cancer is associated with favorable patient outcome.
OBJECTIVE
To investigate the phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal regulated protein kinase (ERK) activation by chemotherapy, and the relationship between the activation of them and patient outcomes. The effect of chemotherapy on the cell proliferation and apoptosis markers and their role in the biology of ovarian cancer were also investigated.


METHODS
This study was carried out in a series of 10 ovarian (or tubal) cancer patients whose specimens were obtained before and after chemotherapy. PI3K-Akt and ERK activation were evaluated by immunohistochemical staining for phosphorylated Akt and ERK. Their correlation with patient outcome was investigated by survival curves using the Kaplan-Meier method. Cell proliferation was evaluated by Ki-67 expression using immunofluorescent staining. Apoptosis was examined by caspase-3 and cleaved Poly ADP ribose polymerase (PARP) using immunofluorescent staining.


RESULTS
An increase in Akt and ERK phosphorylation after chemotherapy was observed in 5 and 8 patients, respectively out of 10 patients examined. Akt and ERK activation by chemotherapy were associated with a favorable overall survival. In almost all patients, Ki-67 expression was initially high and largely decreased after chemotherapy. An increase in apoptotic marker expression was observed in almost all patients exposed to chemotherapy.


CONCLUSIONS
Our findings suggest that Akt and ERK activation by chemotherapy may be associated with favorable prognosis.
Ohta
Tsuyoshi
T
Department of Obstetrics and Gynecology, Yamagata University, Faculty of Medicine, Yamagata 990-9585, Japan. oota-t@med.id.yamagata-u.ac.jp
Isobe
Masanori
M
Takahashi
Toshifumi
T
Saitoh-Sekiguchi
Maki
M
Motoyama
Teiichi
T
Kurachi
Hirohisa
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D019394:Ki-67 Antigen; D009944:Organoplatinum Compounds; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3