Synergism of an antisense oligodeoxynucleotides targeted to hTERT in combination with chemotherapeutic drugs on inhibiting the proliferation of HepG2 cells.
- Author:
Ying YANG
1
;
Qing-you DU
;
Sheng-qi WANG
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; administration & dosage; Cell Line, Tumor; Cisplatin; administration & dosage; DNA-Binding Proteins; Doxorubicin; administration & dosage; Drug Synergism; Fluorouracil; administration & dosage; Humans; Liver Neoplasms; drug therapy; Oligodeoxyribonucleotides, Antisense; administration & dosage; Telomerase; antagonists & inhibitors; genetics
- From: Chinese Journal of Hepatology 2003;11(12):719-721
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSA 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.
RESULTSCombination 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 (
CONCLUSIONASODN may enhance therapeutic effectiveness of chemotherapeutic drugs in human hepatocellular carcinoma cells.