The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells

International Journal of Molecular Sciences

Ye Zhang¹  Xiao-Dong Mu²  En-Zhe Li¹  Ying Luo¹  Na Song¹  Xiu-Juan Qu¹  Xue-Jun Hu² 

[1] Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; E-Mails:;Department of Respiratory Medicine, the First Hospital of China Medical University, Shenyang 110001, China; E-Mail:

关键词: E3 ubiquitin ligase;    β-elemene;    multidrug resistance;    PI3K/Akt;   

DOI  :  10.3390/ijms140510075

来源: mdpi

【 摘 要 】

Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in both K562/DNR and SGC7901/ADR cells and significantly inhibited the expression of P-gp. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c-Cbl and Cbl-b. Importantly, β-elemene significantly enhanced the anti-tumor activity of DOX in nude mice bearing SGC7901/ADR xenografts. Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland