Telomerase inhibition by synthetic nucleic acids and chemosensitization in human bladder cancer cell lines.
The knockdown of genes that are over-expressed in cancer, and function in tumor onset and/or progression, is an attractive tool to impair the growth of tumor cells. Synthetic nucleic acids such as antisense oligodeoxynucleotides (AS-ODNs) or small-interfering RNAs (siRNAs) were applied against different tumor-associated transcripts, including the human telomerase reverse transcriptase (hTERT), to inhibit the proliferation of tumor cells and to sensitize them against chemotherapeutic (CT) agents. The efficacy of nucleic acid-based inhibitors was evaluated in vitro by determining the extent of down-regulation of the respective target mRNA and protein expression as well as by extensively investigating growth properties (e.g., viability, proliferation, apoptosis, and cell-cycle distribution) of the affected tumor cells. Methods for a successful down-regulation of hTERT and for the quantitative determination of resulting effects on cellular growth were described herein.
Kraemer
Kai
K
Department of Urology, Technical University Dresden, Dresdan, Gernany.
Fuessel
Susanne
S
Meye
Axel
A
D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004794:Enzyme Repression / Q000187:drug effects; D005453:Fluorescence; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase