Jung Gwon-Ryul, Kim Kyung-Jong, Choi Cheol-Hee, Lee Tae-Beum, Han Song Iy, Han Hyo-Kyung, Lim Sung-Chul
Department of Pharmacology, College of Medicine, Chosun University, 488 Seosuk-dong, Dong-gu, Gwangju 501-140, Korea.
Basic Clin Pharmacol Toxicol. 2007 Oct;101(4):277-85. doi: 10.1111/j.1742-7843.2007.00115.x.
Primary or acquired resistance of tumours to established chemotherapeutic regimens is a major concern in oncology. Attempts to improve the survival of cancer patients largely depend on strategies to prevent tumour cell resistance. 5-Fluorouracil (5-FU)-based chemotherapy with a combination of other drugs such as irinotecan (IRT) and oxaliplatin (OXT) has been reported to be effective, even though an optimal regimen has yet to be defined due to the relatively high toxicity of the procedure. The aim of this study was to examine the effect of betulinic acid (BetA) as a chemosensitizer for anticancer drug treatment in chemoresistant colon cancer cell lines. A chemoresistant cell line to 5-fluorouracil (SNU-C5/5FU-R), irinotecan (SNU-C5/IRT-R) and oxaliplatin (SNU-C5/OXT-R) treatment were derived from the wild-type colon adenocarcinoma cell line (SNU-C5/WT). The effect of BetA or a combination of anticancer drugs and BetA on the multidrug resistance-related genes, caspases, Bcl-2, Bad and cell death in the SNU-C5/WT and SNU-C5/R cell lines was analysed. BetA alone was an effective chemotherapeutic drug for the SNU-C5/WT, SNU-C5/5FU-R and SNU-C5/OXT-R cells. The combination of BetA with IRT or OXT was effective against SNU-C5/5FU-R cells, and the combination of BetA with 5-fluorouracil, IRT or OXT was effective against SNU-C5/OXT-R cells. BetA induced cancer cell death by apoptosis through the mitochondrial pathway. These findings indicate that the use of BetA as a chemosensitizer may be a new strategy to enhance the efficacy of chemotherapy. However, further studies will be needed for confirmation.
肿瘤对既定化疗方案的原发性或获得性耐药是肿瘤学中的一个主要问题。提高癌症患者生存率的尝试很大程度上取决于预防肿瘤细胞耐药的策略。据报道，以5-氟尿嘧啶（5-FU）为基础并联合伊立替康（IRT）和奥沙利铂（OXT）等其他药物的化疗是有效的，尽管由于该治疗方法毒性相对较高，尚未确定最佳方案。本研究的目的是检测桦木酸（BetA）作为化学增敏剂在化疗耐药结肠癌细胞系中对抗癌药物治疗的效果。对5-氟尿嘧啶（SNU-C5/5FU-R）、伊立替康（SNU-C5/IRT-R）和奥沙利铂（SNU-C5/OXT-R）治疗耐药的细胞系源自野生型结肠腺癌细胞系（SNU-C5/WT）。分析了BetA或抗癌药物与BetA的组合对SNU-C5/WT和SNU-C5/R细胞系中多药耐药相关基因、半胱天冬酶、Bcl-2、Bad和细胞死亡的影响。单独使用BetA对SNU-C5/WT、SNU-C5/5FU-R和SNU-C5/OXT-R细胞是一种有效的化疗药物。BetA与IRT或OXT联合对SNU-C5/5FU-R细胞有效，BetA与5-氟尿嘧啶、IRT或OXT联合对SNU-C5/OXT-R细胞有效。BetA通过线粒体途径诱导癌细胞凋亡死亡。这些发现表明，使用BetA作为化学增敏剂可能是提高化疗疗效的一种新策略。然而，还需要进一步研究加以证实。
