[Combinative effects of FAP-1 antisense oligonucleotide and carboplatin on apoptosis of ovarian cancer cell SKOV3].
OBJECTIVE
Recent studies have shown that overexpression of Fas associated phosphatase-1 (FAP-1) can been detected in human ovarian cancer cell line SKOV3, suggesting that this overexpression may play an important role in the tumorigenesis and drug resistance of ovarian cancer. This study was designed to explore the effects of fas associated phosphatase-1 antisense oligonucleotide (FAP-1 ASODN) combined with carboplatin on the apoptosis of ovarian cancer cell SKOV3.


METHODS
Antisense oligonucleotide technique was used to transfect FAP-1 ASODN into SKOV3 cells. The expression levels of FAP-1 mRNA of SKOV3 cells with or without FAP-1 ASODN transfection were determined by reverse transcription- polymerase chain reaction (RT-PCR). The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM). The growth and proliferation of SKOV3 cells were observed by MTT assay.


RESULTS
After transfected FAP-1 ASODN for 24 hours, the expression of FAP-1 mRNA in SKOV3 cells was obviously reduced compared with those of the control and FAP-1 SODN transfection groups. When induced apoptosis with 40 microg/ml carboplatin for 24-72 hours, FCM results showed the apoptotic rate of "carboplatin+FAP-1 ASODN" group was higher than those of "carboplatin" group and "ASODN" group (P< 0.05), and the cell cycle was blocked in G1 phase. MTT results showed the cell inhibitory rate of "carboplatin+FAP-1 ASODN" group was 1.5-2 times those of "carboplatin" group and "ASODN" group (P< 0.05); but no significant difference was found between "carboplatin" group and "carboplatin+FAP-1 SODN" group (P >0.05).


CONCLUSIONS
FAP-1 ASODN transfection can suppress the expression of FAP-1 gene in SKOV3 cells and enhance the cell sensitivity to apoptosis induced by carboplatin, which implies that FAP-1 ASODN may reverse the drug resistance in ovarian cancer.
Wang
Bin
B
Department of Obstetrics and Gynecology, 254 Hospital, PLA, Tianjin, 300142, PR China. wangbin3@fmmu.edu.cn
Zheng
Wei-Guo
WG
Xin
Xiao-Yan
XY
Qi
Rong-Yi
RY
Yu
Yue-Cheng
YC
Cao
Yun-Xin
YX
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016190:Carboplatin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D016376:Oligonucleotides, Antisense; D016190:Carboplatin; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases