Abstract
Abstract
Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is refractory to most anticancer drugs. Doxorubicin offers a survival benefit to patients with intermediate hepatocellular carcinoma. However, the favorable therapeutic response to doxorubicin is often associated with severe toxicity. The present research was aimed at developing a strategy of increasing doxorubicin sensitivity so that lower doses may be used without compromising efficacy. Recently, aspirin (ASA) and some other nonsteroidal anti-inflammatory drugs (NSAIDs) have drawn much attention for their protective effects against colon cancer and cardiovascular disease. Several studies also found that regular ASA use is significantly associated with reduced risk of lung cancer. We investigated the effects of ASA on HepG2 human hepatocellular carcinoma cell line. Growth inhibition effect of aspirin was measured by MTT assay. Flow cytometry analysis revealed that aspirin can induce G2/M phase arrest which we observed by the level of cell cycle regulatory proteins and DNA ladder formation indicates apoptosis dose dependently. We found that ASA treatment followed both extrinsic and intrinsic pathways for apoptosis induction. In addition to this, when administered in combination, doxorubicin (DOX) and ASA produced synergistic effect in growth inhibition in human hepatocellular carcinoma cells and induced apoptosis in caspase-dependent pathway. Therefore, clinically achievable concentrations of DOX and ASA used in combination may produce a strong anticancer synergy that warrants investigation as a therapeutic strategy to enhance the efficacy of doxorubicin for treating HCC. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 226.