Telomerase antisense inhibition for the proliferation of endometrial cancer in vitro and in vivo.
The objective of this study was to investigate the antitumor effect of antisense telomerase oligodeoxynucleotides to endometrial cancer cells in vitro and in vivo. Antisense oligodeoxynucleotides (ODNs) against the human telomerase transcripatse (hTERT) synthesized to serve as telomerase inhibitors. Reverse transcription-polymerase chain reaction and 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay were used to test the expression of hTERT messengerRNA (mRNA) and inhibition of cell proliferation in vitro. In vivo, antitumor effects of ODNs or combined with cisplatin were evaluated in endometrial cancer xenograft. Telomerase activity was tested by telomeric repeat amplification protocol. Antisense ODNs could inhibit proliferation of human endometrial cancer cells (HEC-1-A) in vitro, and downregulate the expression hTRET mRNA in a dose- and period-dependent manner. The tumor growth inhibitory rate of low- and high-dose ODNs were 34.20% and 89.21%, and combined group was 75.30%. Telomerase activity was downregulated to 87.32% compared to the control in the ODNs-treated xenograft tumors. Antisense oligonucleotides of hTERT effectively inhibit the growth of endometrial cancer cell line. Telomerase inhibitor might be a new strategy for chemotherapy or chemoprevention in endometrial cancer.
Chen
X J
XJ
Second Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Zheng
W
W
Chen
L L
LL
Chen
Z B
ZB
Wang
S Q
SQ
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use; D016373:DNA, Antisense / Q000235:genetics*; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D016373:DNA, Antisense; D012333:RNA, Messenger; D019098:Telomerase; D002945:Cisplatin