[4-amino-1,8-naphthalimide on the Sensitive effect of arsenic trioxide in hepatocellular carcinoma cells].
OBJECTIVE
To study the effect and mechanism of 4-amino-1, 8-naphthalimide (4-AN) on the sensitive effect of arsenic trioxide (ATO) in hepatocellular carcinoma cells.


METHODS
Hepatocellular carcinoma HepG2 cells were divided into two groups according to whether they were treated with 4-AN or not. Cell viability was evaluated by MTT assay, population doubling experiment and colony formation assay; genic mechanism was explored by 8-OH-dG assay, single cell gel electrophoresis (comet assay) and microriucleus test.


RESULTS
At 2-10 micromol/L concentration of ATO, the cell viability and colony formation efficiency of the combinatio group (4-AN+ATO) were significantly lower than that of the ATO group (P<0.05); moreover, the tail-length (L-Tail) and olive tail moment (OTM) in comet assay were notablely higher than that of the ATO group (P<0.05). At 2-20 micromol/L concentration of ATO, the population doubling time and 8-OH-dG in combination group were significantly higher than that of ATO group (P<0.05). Results from DNA damage repair assay showed that the efficiency of DNA damage repair in combination group was remarkably lower than that of ATO group (P<0.05). At 5-20 micromol/L concentration of ATO, the frequency of micronucleated cells in combination group was significantly higher than that of ATO group (P<0.05).


CONCLUSIONS
4-AN can significantly increase the sensitivity of ATO in treatment with hepatocellular carcinoma cells and prevent DNA damage repair may be a primary mechanism for this effect.
Yang
Y
Li
Qing-ying
QY
Luo
Jian-jun
JJ
Deng
Zun-zhen
ZZ
Zhang
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D053644:Naphthalimides / Q000494:pharmacology*; D010087:Oxides / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001152:Arsenicals; D053644:Naphthalimides; D010087:Oxides; D015363:Quinolones; C086538:4-amino-1,8-naphthalimide; D015057:1-Naphthylamine; D000077237:Arsenic Trioxide