[Antisense oligodeoxynucleotides of human telomerse catalytic sub-unit inhibits telomerase activity and proliferation in SKOV3 and COC1].
OBJECTIVE
To study the effects of antisense oligodeoxynucleotides (ODN) of hEST2 (AODN) on telomerase activity and proliferation in ovarian cancer cell lines SKOV3 and COC1.


METHODS
Antisense and sense human telomerse catalytic sub-unit (hEST2) phosphorothioate (SODN) and random ODN were designed, synthesized and transfected into SKOV3 and COC1 cells by lipofectamine. The expression of hEST2 mRNA and telomerase activity in SKOV3 and COC1 were tested by reverse transcription-polymerase chain reaction and telomeric repeat amplification protocol before and after transfection. The proliferation and growth in SKOV3 and COC1 were also investigated by methyl thiazolyl tetrazolium and growth curve before and after transfection.


RESULTS
AODN could down-regulate the expression of hEST2 mRNA, inhibit telomerase activity and proliferation of ovarian cell lines. The efficiency depends on dose and period of administration. At 48 h, 30 micromol/L AODN had the highest activity. The expression of hEST2 mRNA were declined 54.6% and 44.6% in SKOV3 and COC1 respectively. And also the inhibition of telomerase activity were 47.9% and 42.7% respectively in the two cell lines.


CONCLUSIONS
AODN of hEST2 clearly inhibited the proliferation of ovarian cancer cell lines. hEST2 may thus be a new target of gene therapy in ovarian carcinoma.
Yuan
Bibo
B
Department of Obstetrics and Gynecology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Mi
Ruoran
R
D020134:Catalytic Domain; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase