Downregulation of δ opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug‑resistant human hepatocellular carcinoma cells to 5‑FU.
Downregulation of δ opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug‑resistant human hepatocellular carcinoma cells to 5‑FU.
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DOI：
10.3892/mmr.2015.4511
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发表时间：
2016-01
影响因子：
3.4
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Tang B;Hu Z;Li Y;Yuan S;Wang Z;Yu S;He S
δ阿片受体（DOR）是G蛋白偶联受体家族中第一个克隆的阿片受体。我们前期研究表明DOR参与调节人肝细胞癌（HCC）的发生发展，参与调节HCC细胞的侵袭和转移过程。然而，DOR是否参与HCC耐药的发生和发展尚未见报道，需要进一步阐明。本研究旨在探讨DOR在耐药HCC BEL-7402/5-氟尿嘧啶（BEL/FU）细胞株中的表达水平及其对耐药的影响，初步阐明DOR在HCC耐药中的作用。本研究结果表明，DOR在BEL/FU细胞中高水平表达，且表达水平高于正常肝细胞。当DOR表达被抑制时，耐药HCC细胞的增殖不受影响。然而，当细胞与治疗剂量的5-FU共处理时，BEL/FU细胞的增殖速度明显受到抑制，大量细胞发生凋亡，细胞周期进程被阻止，耐药蛋白的表达水平发生变化。总之，DOR在肝癌耐药细胞中表达上调，其功能状态与肝癌耐药密切相关。因此，DOR可能成为临床治疗耐药HCC的公认靶分子。
δ opioid receptor (DOR) was the first opioid receptor of the G protein-coupled receptor family to be cloned. Our previous studies demonstrated that DOR is involved in regulating the development and progression of human hepatocellular carcinoma (HCC), and is involved in the regulation of the processes of invasion and metastasis of HCC cells. However, whether DOR is involved in the development and progression of drug resistance in HCC has not been reported and requires further elucidation. The aim of the present study was to investigate the expression levels of DOR in the drug-resistant HCC BEL-7402/5-fluorouracil (BEL/FU) cell line, and its effects on drug resistance, in order to preliminarily elucidate the effects of DOR in HCC drug resistance. The results of the present study demonstrated that DOR was expressed at high levels in the BEL/FU cells, and the expression levels were higher, compared with those in normal liver cells. When the expression of DOR was silenced, the proliferation of the drug-resistant HCC cells were unaffected. However, when the cells were co-treated with a therapeutic dose of 5-FU, the proliferation rate of the BEL/FU cells was significantly inhibited, a large number of cells underwent apoptosis, cell cycle progression was arrested and changes in the expression levels of drug-resistant proteins were observed. Overall, the expression of DOR was upregulated in the drug-resistant HCC cells, and its functional status was closely associated with drug resistance in HCC. Therefore, DOR may become a recognized target molecule with important roles in the clinical treatment of drug-resistant HCC.