Yang Ying, Du Qing-you, Wang Sheng-qi
Beijing Institution of Radiation Medicine, Beijing 100850, China.
Zhonghua Gan Zang Bing Za Zhi. 2003 Dec;11(12):719-21.
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.
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.
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.
ASODN may enhance therapeutic effectiveness of chemotherapeutic drugs in human hepatocellular carcinoma cells.
探讨硫代磷酸反义寡脱氧核苷酸“ASOND”分别与顺二氨二氯铂（DDP）、5-氟尿嘧啶（5-FU）和阿霉素（ADM）联合应用对抑制肝癌细胞HepG2增殖的影响。
合成针对人端粒酶逆转录酶（hTERT）mRNA的硫代磷酸反义寡脱氧核苷酸（5'-ACTCACTCAGGCCTCAGACT-3'），命名为甘肽。采用脂质体法将ASODN转染至HepG2细胞。通过MTT法评估细胞生长活性。运用SAS软件和金正均法评估ASODN与这些化疗药物的相互作用。
0.1μmol/L ASODN联合用药分别使DDP、5-FU和ADM的IC50从1.07、4.15和0.29μg/ml降至0.25、1.52和0.12μg/ml。联合用药对HepG2细胞的抑制能力高于各药物单独使用时（F = 66.92、25.96、8.56，P < 0.001）。在较低浓度的DDP（≤1μg/ml）、5-FU（≤10μg/ml）和ADM（≤0.1μg/ml）与ASODN联合使用时观察到协同作用（Q≥1.15）。
ASODN可能增强化疗药物对人肝癌细胞的治疗效果。
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