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. 2019 Jun;10(6):1469-1478.
doi: 10.1111/1759-7714.13096. Epub 2019 May 23.

Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells

Hongxia Shang  1 , Shengnan Wang  2 , Jinming Yao  1 , Congcong Guo  1 , Jianjun Dong  3 , Lin Liao  1
Affiliations

Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells

Hongxia Shang et al. Thorac Cancer. 2019 Jun.

Abstract

Background: No effective treatment is currently available for poorly differentiated thyroid cancer which is resistant to radioiodine, especially with migration and invasion. A great number of researches have revealed the anticancer effects of salidroside, but none have studied the effects of salidroside on thyroid cancer. This study aimed to investigate the effect of salidroside on migration and invasion of poorly differentiated thyroid cancer cells.

Methods: The effects of salidroside on migration, invasion and apoptosis of poorly differentiated thyroid cancer WRO cells and normal thyroid follicular epithelial Nthy-ori 3-1 cells were measured by wound-healing assay, transwell migration/invasion assay and flow cytometry, respectively. The expression levels of MMP2 and MMP9 at RNA and protein levels in WRO cells were detected by qRT-PCR and western blot. The phosphorylation levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and the apoptosis-related protein levels of Bax, cleaved caspase 3 and Bcl-2 were assessed by western blot.

Results: Salidroside significantly suppressed migration/invasion and induced apoptosis in poorly differentiated thyroid cancer WRO cells. We further illustrated that salidroside significantly inhibited expressions of MMP2 and MMP9 at mRNA and protein levels and the phosphorylation activation of JAK2/STAT3 in WRO cells. In addition, salidroside increased expressions of pro-apoptotic factors (Bax and cleaved caspase 3) and decreased expression of anti-apoptotic factor (Bcl-2) significantly in WRO cells.

Conclusion: The present study demonstrates that salidroside inhibits migration and invasion of WRO cells (a kind of poorly differentiated cancer cell line) significantly, which might be via suppressing JAK2-STAT3 signaling pathway.

Keywords: Invasion; migration; poorly differentiated thyroid cancer; salidroside.

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Figures

Figure 1
Figure 1
Salidroside inhibited the migration of poorly differentiated thyroid cancer WRO cells. Cell migration of normal thyroid follicular epithelial Nthy‐ori 3‐1 cells and poorly differentiated thyroid cancer WRO cells was detected by wound‐healing assay (a) and transwell migration assay (b). (c) The histogram shows the results of the quantitative analysis of transwell migration assay. Data are shown as the mean ± SD of three experiments. *P < 0.05 versus control.
Figure 2
Figure 2
Salidroside inhibited the invasion of poorly differentiated thyroid cancer WRO cells. (a) Cell invasion of normal thyroid follicular epithelial Nthy‐ori 3‐1 cells and poorly differentiated thyroid cancer WRO cells was detected by transwell invasion assay. (b) The histogram below shows the results of the quantitative analysis of transwell invasion assay. Data are shown as the mean ± SD of three experiments. *P < 0.05 versus control.
Figure 3
Figure 3
Salidroside down‐regulated the expressions of MMP2 and MMP9 at mRNA and protein levels in poorly differentiated thyroid cancer WRO cells. (a) The mRNA expressions of MMP2 and MMP9 were detected by quantitative real‐time PCR. (b) The protein expressions of MMP2 and MMP9 were detected by western blot. (c) The histogram below shows the results of the quantitative analysis of changes in MMP2 and MMP9 protein expression. Data are shown as the mean ± SD of three experiments. *P < 0.05 versus control.
Figure 4
Figure 4
Salidroside inhibited the phosphorylation activation of JAK2 ‐STAT3 signaling pathway. (a) The phosphorylation of JAK2 and STAT3 were determined by western blot analysis and represented by the ratio of pJAK2/JAK2 and pSTAT3/STAT3. (b) The histogram below shows the results of the quantitative analysis of changes in phosphorylation of JAK2 and STAT3. Data are shown as the mean ± SD of three experiments. *P < 0.05 versus control.
Figure 5
Figure 5
Salidroside induced apoptosis in poorly differentiated thyroid cancer WRO cells. (a) The apoptotic cells were detected by Annexin V‐FITC and PI staining using flow cytometry with normal thyroid follicular epithelial Nthy‐ori 3‐1 cells and poorly differentiated thyroid cancer WRO cells. The percentage of apoptotic cells is shown as the mean ± SD above the panels. (b) The histogram below shows the results of the quantitative analysis. Data are shown as the mean ± SD of three experiments. *P < 0.05 versus control. (c) The protein expression of Bax, cleaved caspase 3 and Bcl‐2 was detected by western blot. (d) The histogram shows the results of the quantitative analysis of changes in Bax, cleaved caspase 3 and Bcl‐2 protein expression. Data are shown as the mean ± SD of three experiments. *P < 0.05 versus control.
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