Thalidomide inhibits proliferation and epithelial-mesenchymal transition by modulating CD133 expression in pancreatic cancer cells

Abstract

Pancreatic cancer is a solid malignancy with a high mortality rate, on account of the high incidence of metastasis at the time of detection. The aggressiveness of pancreatic cancer may be partly driven by cancer stem cells (CSCs), which are characterized by the ability to self-renew and recapitulate tumors in the ectopic setting. However, although a number of drugs targeting CSCs are currently under clinical investigation, few effective drugs have been developed. The present study demonstrated that thalidomide inhibited cell proliferation and metastasis in pancreatic cancer cell lines through the inhibition of epithelial mesenchymal transition. The effect of thalidomide was more pronounced in cluster of differentiation 133 (CD133)+ SW1990 cells than in Capan-2 cells, in which CD133 expression was almost undetectable. The results revealed that CD133 is likely to serve a role in the antitumor effect of thalidomide and indicated that thalidomide could be developed as a CSC-specific adjuvant chemotherapy in pancreatic cancer.

Keywords: cancer stem cells; cluster of differentiation 133; epithelial-mesenchymal transition; metastasis; pancreatic cancer; proliferation; thalidomide.

Figures

Figure 1.

Thalidomide inhibits the cell viability of pancreatic cancer cell lines. The viability of (A) Capan-2 and (B) SW1990 cells treated with a range of thalidomide concentrations was measured with an MTT assay and compared with untreated cells. Thalidomide treatment induced a dose- and time-dependent inhibitionof cell viability. Results represent the mean ± standard deviation from six independent experiments.

Figure 2.

The effect of thalidomide on the migration of pancreatic cancer cell lines was assessed using Transwell filter inserts. (A) The relative proportion of migrated pancreatic cancer cells treated with thalidomide for 48 h was determined. Magnification, ×200. (B) Analysis of cell migration. *P

Figure 3.

Flow cytometry analysis of the proportion of CD133+ cells in the Capan-2 and SW1990 cell lines following treatment with different concentrations of thalidomide. (A) Capan-2 cells were 0.2% CD133+, compared with 41.3% for SW1990 cells. (B) Thalidomide treatment reduced the CD133+ cell subpopulation in SW1990 cells; however, there was no effect on Capan-2 cells. *P<0.05 compared with NC. CD133, cluster of differentiation 133; NC, negative control.

Figure 4.

Thalidomide inhibited EMT and downregulated CD133 expression in SW1990 cells. The expression levels of E-cad, N-cad and CD133 were detected by (A) reverse transcription-quantitative polymerase chain reaction and (B) western blotting. Thalidomide downregulated CD133 and N-cad mRNA and protein expression and upregulated E-cad mRNA and protein expression in SW1990 cells; however, it had no effect on the levels of these markers in Capan-2 cells. *P