Involvement of the TGFβ1/Smad2/MMP3 signaling pathway in SB431542-induced inhibition of cell invasion in multiple myeloma RPMI 8226 cells.
ONCOLOGY LETTERS(2017)
摘要
Multiple myeloma (MM) is a malignancy characterized by plasma cell hyperplasia. The majority of patients with MM suffer from mortality due to tumor recurrence and metastasis, which has become an emerging clinical problem. Transforming growth factor beta 1 (TGF beta 1) has been implicated in tumor metastasis; however, its role in RPMI 8226 cells remains to be elucidated. In the present study, RPMI 8226 cells were treated with various concentrations of SB431542, a TGF beta 1 inhibitor, for 12, 24 and 48 h. RPMI 8226 cells were transfected with lentiviral-TGF beta 1 vectors to overexpress TGF beta 1. Cell proliferation rate was subsequently determined by cell-counting kit-8 assay and cell invasion was assessed by Transwell assay. Expression of TGF beta 1, SMAD family member 2 (Smad2) and matrix metallopeptidase 3 (MMP3) were analyzed by western blotting. The results demonstrated that cell proliferation and invasion of RPMI 8226 cells was significantly inhibited by SB431542 (P<0.05). SB431542 was able to significantly downregulate the expression of TGF beta 1, phosphorylated (p)-Smad2 and MMP3; however, the overexpression of TGF beta 1 significantly upregulated the expression of TGF beta 1, p-Smad2 and MMP3. In conclusion, SB431542 reduced cell invasion in RPMI 8226 cells, and this effect may be mediated via the TGF beta 1/Smad2/MMP3 signaling pathway.
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关键词
multiple myeloma,transforming growth factor beta 1,SMAD family member 2,matrix metallopeptidase 3,cell invasion
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