[Synergism of an antisense oligodeoxynucleotides targeted to hTERT in combination with chemotherapeutic drugs on inhibiting the proliferation of HepG2 cells].
OBJECTIVE
To investigate the effect of a phosphorothioate antisense oligodeoxynucleotide "ASOND" combined with cis-Diamminedichloroplatinum (DDP), 5-fluorouracil (5-FU) and adriamycin (ADM) respectively on inhibiting the proliferation of HepG2 cells.


METHODS
A phosphorothioate antisense oligodeoxynucleotide (5'-ACTCACTCAGG CCTCAGACT-3') targeted to human telomerase reverse transcriptase (hTERT) mRNA, which named cantide, was synthesized. ASODN was transfected into HepG2 by lipofectin. And cell growth activity was evaluated by MTT assay. SAS software and Jin Zhengjun Method were used to evaluate the interaction of ASODN and these chemotherapeutic drugs.


RESULTS
Combination treatments with 0.1micromol/L ASODN reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29microg/ml to 0.25, 1.52 and 0.12microg/ml respectively. The inhibitory ability of combination treatments on HepG2 cells was higher than that of these drugs alone (F=66.92, 25.96, 8.56, P<0.001). And synergism (Q>or=1.15) was observed at the lower concentration of DDP (<or=1microg/ml), 5-FU (<or=10microg/ml) and ADM (<or=0.1microg/ml) with combination of ASODN.


CONCLUSIONS
ASODN may enhance therapeutic effectiveness of chemotherapeutic drugs in human hepatocellular carcinoma cells.
Yang
Ying
Y
Beijing Institution of Radiation Medicine, Beijing 100850, China.
Du
Qing-you
QY
Wang
Sheng-qi
SQ
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D004317:Doxorubicin; D019098:Telomerase; D002945:Cisplatin; D005472:Fluorouracil