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Yan W, Tu B, Liu YY, et al. Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions. Bone Res. 2013;1(4):362-70doi: 10.4248/BR201304007.
Yan, W., Tu, B., Liu, Y. Y., Wang, T. Y., Qiao, H., Zhai, Z. J., Li, H. W., & Tang, T. T. (2013). Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions. Bone research, 1(4), 362-70. https://doi.org/10.4248/BR201304007
Yan, Wei, et al. "Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions." Bone research vol. 1,4 (2013): 362-70. doi: https://doi.org/10.4248/BR201304007
Yan W, Tu B, Liu YY, Wang TY, Qiao H, Zhai ZJ, Li HW, Tang TT. Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions. Bone Res. 2013 Dec 31;1(4):362-70. doi: 10.4248/BR201304007. eCollection 2013 Dec. PMID: 26273514; PMCID: PMC4472116.
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Bone Res. 2013 Dec 31;1(4):362-70. doi: 10.4248/BR201304007. eCollection 2013 Dec.

Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions.

Bone research

Wei Yan, Bing Tu, Yun-Yun Liu, Ting-Yu Wang, Han Qiao, Zan-Jing Zhai, Hao-Wei Li, Ting-Ting Tang

Affiliations

  1. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011, China ; Wendeng Zhenggu Hospital of Shandong Province , Wendeng, Shandong 264400, China.
  2. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011, China.
  3. Department of Gynecology and Obstetrics, Wendeng Center Hospital of Weihai City , Weihai, Shandong 264400, China.
  4. Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, 200011 China.

PMID: 26273514 PMCID: PMC4472116 DOI: 10.4248/BR201304007

Abstract

OBJECTIVE: The aim of this study was to investigate the effects of plumbagin (PL), a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells.

METHODS: Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plumbagin for 24 h. The effects of plumbagin on the migration and invasion were observed by a transwell method. The expressions of IL-1α, IL-1β, IL-6, IL-8, TGF-β, TNFα, MMP-2 and MMP-9 mRNA in MDA-MB-231SArfp cells were detected using Real-Time PCR. MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes. The activation of STAT3 was detected by western blot. Following this analysis, STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA. mRNA levels of IL-1α, TGF-β, MMP-2 and MMP-9 were then detected. Consequently, MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model. The mice were injected intraperitoneally with plumbagin. Non-invasive in vivo monitoring, X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo.

RESULTS: The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1α, TGF-β, MMP-2 and MMP-9. Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB-231SArfp cells. The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1α, TGF-β, MMP-2 and MMP-9. In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases, as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions.

CONCLUSIONS: Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and by downregulation of IL-1α, TGF-β, MMP-2 and MMP-9.

Keywords: breast cancer; invasion; migration; plumbagin

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