Survivin status affects prognosis and chemosensitivity in epithelial ovarian cancer.
OBJECTIVE
The objective of this study was to explore the clinical significance of survivin expression in epithelial ovarian cancer (EOC) and the effect of survivin small hairpin RNA (shRNA) on survivin expression, apoptosis, and chemosensitivity in the human ovarian cancer cell line OVCAR3.


METHODS
A retrospective review of 90 consecutive EOC patients with a median follow-up time of 51 months was conducted. Survivin expression was examined by immunohistochemistry. OVCAR3 cells were transfected in vitro with survivin shRNA. Survivin mRNA expression levels were detected using reverse transcription-polymerase chain reaction. Flow cytometry was applied to determine survivin protein expression levels and cell apoptotic rates. The MTT method was used to examine the effects of survivin shRNA on chemosensitivity in OVCAR3 cells.


RESULTS
Positive cytoplasmic expression of survivin was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, nonmucinous type, high grade, and recurrence. Positive survivin expression was also associated with platinum resistance (r = 0.306, P = 0.003). Statistical results indicated that FIGO stage (hazard rate = 1.649, P = 0.047) and cytoplasmic expression of survivin (hazard rate = 1.734, P = 0.010) were independent prognostic factors. Survivin mRNA and protein levels were lower in OVCAR3S (ovarian cancer cells transfected with a survivin recombinant vector) cells at 24 hours after transfection as compared with controls. The flow cytometric analysis revealed that survivin shRNA induced accumulation of cells in the G0/Gl phase, with a decrease in G2/M phase cells following 24 hours of culture as compared with a nontransfected group (P < 0.01). Furthermore, survivin shRNA increased the sensitivity of OVCAR3 cells to paclitaxel 15-fold (P < 0.05), whereas it had no significant effect on cisplatin (P > 0.05).


CONCLUSIONS
In addition to FIGO stage, cytoplasmic survivin protein expression is an independent molecular marker for predicting EOC prognosis. Sequence-specific shRNA targeting survivin can effectively suppress survivin expression, enhance apoptosis, and increase the sensitivity of ovarian cancer cells to paclitaxel but not to cisplatin.
Department of Gynecology, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
Lifeng
L
Chen
Lizhi
L
Liang
Xiaojian
X
Yan
Naihua
N
Liu
Lihua
L
Gong
Shishi
S
Pan
Feng
F
Lin
Qian
Q
Zhang
Hongqin
H
Zhao
Feiyun
F
Zheng
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology; D012189:Retrospective Studies; D000077022:Survivin; D055815:Young Adult
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D017239:Paclitaxel