Antisense telomerase induced cell growth inhibition, cell cycle arrest and telomerase activity down-regulation in gastric and colon cancer cells.

Abstract

BACKGROUND: Antisense telomerase RNA (anti-hTR) coupled with 2',5'-linked tetraadenylate (2-5A) shows an inhibitory effect on cell growth and induces apoptosis in certain kinds of cancer. This experiment examined the anti-hTR effect on gastric and colorectal cancer cells. MATERIALS AND METHODS: Gastric cancer cells CRL-5822, CRL-5971 and colorectal cancer cells HTB-38, CCL-247 were treated with repeated doses of anti-hTR. Cell growth and cell cycle parameters were analysed. Telomerase activity was measured by TRAP assay. Control oligonucleotides and normal fibroblast were used as control. RESULTS: After two doses of anti-hTR, the cell viability for CRL-5822, CRL-5971, HTB-38 and CCL-247 cells was reduced to 15%, 12%, 37% and 37%, respectively. The DNA histogram showed cells arrested at the G2/M-phase and the sub-G1 peak found indicated that apoptosis had occurred. CONCLUSION: Anti-hTR demonstrated inhibition of cell growth and cell cycle arrest on gastric and colorectal cancer cells through a telomerase regulation pathway. Its specificity towards cancerous tissues but not normal tissues suggested a potential for anti-cancer therapy.