Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α.

Jiang Qian,Sheliang Shen,Wei Chen,Nianping Chen

doi:10.1155/2018/4174232

Abstract

Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia-induced epithelial–mesenchymal transition (EMT), driven by hypoxia-inducible factor 1α (HIF-1α), is involved in cancer progression and metastasis. The present study was designed to explore the role of propofol in hypoxia-induced resistance of prostate cancer cells to docetaxel. We used the Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine incorporation assay to measure cell viability and cell proliferation, respectively, in prostate cancer cell lines. Then, we detected HIF-1α, E-cadherin, and vimentin expression using western blotting. Propofol reversed the hypoxia-induced docetaxel resistance in the prostate cancer cell lines. Propofol not only decreased hypoxia-induced HIF-1α expression, but also reversed hypoxia-induced EMT by suppressing HIF-1α. Furthermore, small interfering RNA–mediated silencing of HIF-1α reversed the hypoxia-induced docetaxel resistance, although there was little change in docetaxel sensitivity between the hypoxia group and propofol group. The induction of hypoxia did not affect E-cadherin and vimentin expression, and under the siRNA knockdown conditions, the effects of propofol were obviated. These data support a role for propofol in regulating EMT in prostate cancer cells. Taken together, our findings demonstrate that propofol plays an important role in hypoxia-induced docetaxel sensitivity and EMT in prostate cancer cells and that it is a potential drug for overcoming drug resistance in prostate cancer cells via HIF-1α suppression.

Highlights

Hypoxia is common in the microenvironment of solid tumors and is associated with tumor invasion, distant metastasis, and epithelial–mesenchymal transition (EMT) [1,2,3]
We found that propofol could reverse hypoxia-induced docetaxel resistance in prostate cancer cells by reversing EMT via hypoxia-inducible factor 1α (HIF-1α) inhibition
Cell viability was significantly increased in hypoxic conditions compared with normoxia (Figures 1(a)–1(c), Table 1), confirming that hypoxia induces docetaxel resistance in prostate cancer cells

Summary

Introduction

Hypoxia is common in the microenvironment of solid tumors and is associated with tumor invasion, distant metastasis, and epithelial–mesenchymal transition (EMT) [1,2,3]. HIF-1α is the most important hypoxia-induced transcription factor and has multiple functions in tumor progression, including changes in the aggressive behavior of the tumor [6]. HIF-1α plays a role in prostate cancer cell EMT and migration [7]. EMT is characterized by the combined loss of epithelial cell junction proteins such as E-cadherin and the gain of mesenchymal markers such as vimentin or fibronectin [9]. It has become increasingly clear over recent years that EMT, a critical developmental process, plays a major role in cancer progression [10, 11]. Docetaxel has been considered standard firstline therapy in prostate cancer cases [14]; it confers only a modest survival advantage, as patients eventually

Methods

Results

Conclusion