Total glucosides of paeony inhibits lipopolysaccharide-induced proliferation, migration and invasion in androgen insensitive prostate cancer cells.

Zhi-Hui Zhang,Dong-Dong Xie,Shen Xu,Hao Geng,Zhi-Qiang Zhang,Wei Wei,Lei Chen,De-Xin Yu,De-Xiang Xu,Mi-Zhen Xia,Da-Ming Wang,Salvatore V Pizzo

doi:10.1371/journal.pone.0182584

Abstract

Previous studies demonstrated that inflammatory microenvironment promoted prostate cancer progression. This study investigated whether total glucosides of paeony (TGP), the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS)-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells. PC-3 cells were incubated with LPS (2.0 μg/mL) in the absence or presence of TGP (312.5 μg /mL). As expected, cells at S phase and nuclear CyclinD1, the markers of cell proliferation, were increased in LPS-stimulated PC-3 cells. Migration activity, as determined by wound-healing assay and transwell migration assay, and invasion activity, as determined by transwell invasion assay, were elevated in LPS-stimulated PC-3 cells. Interestingly, TGP suppressed LPS-stimulated PC-3 cells proliferation. Moreover, TGP inhibited LPS-stimulated migration and invasion of PC-3 cells. Additional experiment showed that TGP inhibited activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)/p38 in LPS-stimulated PC-3 cells. Correspondingly, TGP attenuated upregulation of interleukin (IL)-6 and IL-8 in LPS-stimulated PC-3 cells. In addition, TGP inhibited nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in LPS-stimulated PC-3 cells. These results suggest that TGP inhibits inflammation-associated STAT3 activation and proliferation, migration and invasion in androgen insensitive prostate cancer cells.

Highlights

In Western countries, prostate cancer is one of the most common malignant tumors in men [1]
This study investigated whether total glucosides of paeony (TGP), the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS)-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells
TGP inhibited nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in LPS-stimulated PC-3 cells. These results suggest that TGP inhibits inflammation-associated STAT3 activation and proliferation, migration and invasion in androgen insensitive prostate cancer cells

Summary

Introduction

In Western countries, prostate cancer is one of the most common malignant tumors in men [1]. In China, the rate of prostate cancer is rapidly increasing and especially in patients with obesity or diabetes [3,4]. As androgen receptor plays an important role in the pathogenesis of prostate cancer, androgen-deprivation therapy remains the principal method for treatment of patients with prostate cancer [5]. Several studies demonstrate that inflammatory microenvironment promotes prostate cancer development and progression [7,8,9]. Nuclear factor kappa B (NF-κB) and nuclear translocation of signal transducer and activator of transcription (STAT) play important roles in the pathogenesis of inflammation-associated progression of prostate cancer

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