항암제내성 대장암세포에 대한 betulinic acid의 치료상승효과

Abstract

Primary or acquired resistance of tumors to established chemotherapeutic regimens still constitutes a big concern in oncology. Thus, attempts to improve the survival of cancer patients largely depend on strategies to target tumor cell resistance. The aim of this study was to investigate the effect of betulinic acid (BetA) as a chemosensitizer in anticancer drug treatment of chemoresistant colon cancer cell lines. Chemoresistant sublines against 5-FU (SNU-C5/5FU-R), IRT (SNU-C5/IRT-R), and OXT (SNU-C5/OXT-R) were made from the wild type of colon adenocarcinoma cell line SNU-C5. To analyze the role and effect of BetA in SNU-C5 and SNU-C5/R cell lines, the author carried out MTT assay, Western blot analysis, PI staining, Hoechst staining, and DNA fragmentation test. BetA alone was a good chemotherapeutic drug for SNU-C5, SNU-C5/5FU-R, and SNU-C5/OXT-R cells. Combination of BetA with IRT or OXT was effective in the SNU-C5/5FU-R cells, and combination of BetA with 5-FU, IRT or OXT was effective in the SNU-C5/OXT-R cells. The role of BetA on cancer cell death was induction of apoptosis through mitochondrial pathway. BetA alone or in combination with anticancer drugs worked in concert to induce activation of caspases and then apoptosis in some cell lines resistant to different anticancer drugs. These findings indicate that utility of BetA as a chemosensitizer in chemotherapy may be a new strategy to enhance the efficacy of chemotherapy, which warrants further investigation.