[The Experiment Study and Mechanism of Aspirin Enhances Cellular Sensitivity of Hepatocellular Carcinoma Cell Line to Arsenic Trioxide].
OBJECTIVE
To explore whether aspirin could sensitize arsenic trioxide on human hepatocelluar carcinoma cell line and understanding the combination mechanisms underlying co-treatment.


METHODS
Cell viability was detected by MTT assay, cell apoptosis rate and reactive oxygen species (ROS) level were measured by flow cytometry, and Western blot assay was used to estimated the protein expression of heme oxygenase-1 (HO-1) in total protein and NF-E2-related factor 2 (Nrf2) in nuclear protein.


RESULTS
10 μmol/L arsenic trioxide can decreased the cell viability, while cell apoptosis rate, ROS level, HO-1 and Nrf2 protein expression was increased (P < 0.05). When compared with arsenic trioxide alone, co-treatment of arsenic trioxide with aspirin in different concentration (0, 0.1, 1.0, 2.5, 5.0 mmol/L) exhibited dual effects in intracellular ROS level, HO-1 and Nrf2 expression. Specifically, with the increasing of aspirin concentrations, the level of ROS induced by arsenic trioxide showed a rising trend after the first reduction, whereas, HO-1 and Nrf2 protein expression were decreased at first and then increased.


CONCLUSIONS
Low concentration, less than 2.5 mmol/L, of aspirin may reduce the ROS accumulation through activating of Nrf2-HO-1 pathway, therefore decreasing the apoptotic cell death induced by arsenic trioxide. On the contrary, 5 mmol/L aspirin could increase the sensitivity of HepG2 to arsenic trioxide through enhancing the arsenic trioxide-induced apoptosis by ROS accumulation resulting in inhibiting the Nrf2-HO-1 pathway.
Ya-nan
YN
Hu
Shi-yan
SY
Gu
Zun-zhen
ZZ
Zhang
D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001241:Aspirin / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010087:Oxides / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
D001152:Arsenicals; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010087:Oxides; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001241:Aspirin; D000077237:Arsenic Trioxide