Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells

• DOI: 10.18632/oncotarget.20194
• Publication Date: 2017-08-12T10:18:14Z
• Authors: Qie Guo; Zhong-Guo Sui; Wen Xu; Xiang-Hua Quan; Jia-Lin Sun; Xiao Li; Hong-Yan Ji; Fan-Bo Jing
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Research Paper; 3. Good health

Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid progression and high mortality. However, chemotherapy HCC hindered by multi-drug resistance (MDR). It urgent, therefore, to explore new approaches for overcoming MDR cells. Ubenimex, an inhibitor CD13, has been used as immuno-enhancer treating hematological neoplasms other solid tumors. Here, we demonstrate that Ubenimex can also reverse in cell lines HepG2/5-FU Bel7402/5-FU. inhibits expression proto-oncogene, Pim-3, which accompanied decreased BCL-2 BCL-XL, phosphorylation Bad, increased tumor apoptosis. Moreover, decreases MDR-associated proteins P-gp, MRP3 MRP2 enhance intracellular accumulation Cisplatin, down-regulation Pim-3 essential. Our results reveal a previously uncharacterized function mediating drug HCC, suggests may provide strategy improve sensitivity chemotherapeutic drugs via its effects on Pim-3.