State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China.
J Sci Food Agric. 2012 Jan 15;92(1):135-40. doi: 10.1002/jsfa.4551. Epub 2011 Jul 21.
Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its reversal effects on cancer cell MDR.
A human hepatocellular tumor xenograft model was established with the BEL-7402/5-FU cell line. Combined 5-fluorouracil (5-FU) and DMC (40 mg kg(-1) ) treatment significantly elevated tumor inhibition rate to 72.2%. DMC could also increase 5-FU concentrations in tumor tissues and increase caspase-3 activity. Also, combined therapy resulted in enhanced tumor apoptotic and reduced proliferative activities relative to 5-FU alone. Examining body weight and other signs of unwanted toxicity of the different treatment groups revealed no significant signs of adverse effects.
All results suggested that DMC reverses 5-FU resistance, with a benign side effects profile.
多药耐药性（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）从桃金娘科的闭鞘姜（Cleistocalyx operculatus（Roxb.）Merr. et Perry）的芽中分离出来，研究了其对癌细胞 MDR 的逆转作用。
用人肝癌 BEL-7402/5-FU 细胞系建立了人肝癌异种移植模型。联合使用 5-氟尿嘧啶（5-FU）和 DMC（40 mg kg（-1））治疗可使肿瘤抑制率显著提高至 72.2%。DMC 还可以增加肿瘤组织中 5-FU 的浓度并增加 caspase-3 的活性。此外，与单独使用 5-FU 相比，联合治疗导致肿瘤凋亡增加和增殖活性降低。检查不同治疗组的体重和其他不良毒性迹象，未发现明显的不良反应迹象。
所有结果均表明 DMC 逆转了 5-FU 耐药性，且具有良性的副作用特征。
