HNF-4α promotes multidrug resistance of gastric cancer cells through the modulation of cell apoptosis

作者：Ma, Yubo; Wei, Xufu; Wu, Zhongjun^*

来源：Oncology Letters, 2017, 14(6): 6477-6484.

DOI：10.3892/ol.2017.7095

• apoptosis
• B-cell lymphoma 2
• gastric cancer
• hepatocyte nuclear factor-4 alpha
• multidrug resistance
• transcription factor

Multidrug resistance (MDR) typically leads to treatment failure, and is associated with disease progression of gastric cancer (GC). In the present study, a total of 15 aberrantly activated transcription factors (TFs) were detected in chemo-resistant GC cells using a TF Activation Profiling Plate Array. Among these TFs, hepatocyte nuclear factor (HNF)-4 alpha was significantly upregulated in multidrug-resistant GC cells (P=0.019). The overexpression of HNF-4 alpha was able to cause resistance to multiple chemotherapeutics, whereas inhibition of HNF-4 alpha appeared to reverse cancer cell resistance. Further studies demonstrated that HNF-4 alpha had no clear influence on drug transportation; however, inhibition of drug-induced cell apoptosis occurred as B-cell lymphoma 2 (Bcl-2) expression increased in GC cells. Additionally, immunohistochemistry demonstrated that HNF-4 alpha was overexpressed in human GC tissues, and associated with tumor stage and lymph node metastasis. In conclusion, the results of the present study indicate the involvement of TFs in MDR in GC, and suggest that HNF-4 alpha may enhance MDR in GC by regulating cell apoptosis and Bcl-2 expression.

• 出版日期2017-12
• 单位重庆医科大学