State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China.
Phytomedicine. 2011 Sep 15;18(12):1086-92. doi: 10.1016/j.phymed.2011.04.001. Epub 2011 May 18.
Multi drug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a chalcone, isolated from the buds of Cleistocalyx operculatus, has been shown to have antitumor effects on human carcinoma SMMC-7721 cells in vitro and in vivo. In this paper, we studied the reversal effect and the mechanism of DMC on human hepatocellular carcinoma drug-resistant cells BEL-7402/5-FU in vitro. Administration of DMC reversed the multi-drug resistance of human hepatocellular carcinoma BEL-7402/5-FU cells significantly. DMC enhanced the sensitivity of BEL-7402/5-FU cells to 5-fluorouracil (5-FU) and doxorubicin (DOX). Staining with Hoechst 33258 and flow cytometric analysis showed that DMC has apoptosis-inducing effect on BEL-7402/5-FU cells. It could also increase the concentration of 5-FU in the resistant multi-drug-resistant cells. We also observed that over-expression of the multi-drug resistance-associated protein (MRP1) and of the glutathione S-transferase π (GST-π) contributed to MDR in BEL-7402/5-FU cells. The mRNA expressions of MRP1 and GST-π and the protein expression of MRP1 were decreased by DMC. These data demonstrated that DMC could effectively reverse MDR in BEL-7402/5-FU cells.
多药耐药（MDR）是许多人类癌症化疗治疗的主要障碍。2'，4'-二羟基-6'-甲氧基-3'，5'-二甲基查尔酮（DMC），一种从糯米团芽中分离出来的查尔酮，已被证明对体外和体内人肝癌 SMMC-7721 细胞具有抗肿瘤作用。在本文中，我们研究了 DMC 对体外人肝癌耐药细胞 BEL-7402/5-FU 的逆转作用及其机制。DMC 给药显著逆转了人肝癌 BEL-7402/5-FU 细胞的多药耐药性。DMC 增强了 BEL-7402/5-FU 细胞对 5-氟尿嘧啶（5-FU）和阿霉素（DOX）的敏感性。Hoechst 33258 染色和流式细胞术分析表明，DMC 对 BEL-7402/5-FU 细胞具有诱导凋亡作用。它还可以增加耐药多药耐药细胞中 5-FU 的浓度。我们还观察到多药耐药相关蛋白（MRP1）和谷胱甘肽 S-转移酶π（GST-π）的过度表达有助于 BEL-7402/5-FU 细胞的 MDR。DMC 降低了 MRP1 和 GST-π 的 mRNA 表达和 MRP1 的蛋白表达。这些数据表明 DMC 可以有效逆转 BEL-7402/5-FU 细胞的 MDR。
