摘要
Objective： To explore the effects of Janus activated kinase （JAK） inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase （ERK） in human breast cancer cells MDA-MB-231 and the roles of JAK in the invasion and metastasis of the human breast cancer cells through ERK signaling transduction pathways. Methods： MDA-MB-231 cells were treated with 20 μmol/L, 40 μmol/L, 80 μmol/L Janus kinase inhibitor AG490 for 24, 48 and 72 h. Proliferation and adhesion of MDA-MB-231 cells to matrigel were measured with MTT assay. When treated with 40 μmol/L AG490 for 24 h, the expressions of P-ERK and MMP-9 of cells were detected by Western-blot and invasion and metastasis of MDA-MB-231 cells were evaluated with transwell chamber. Results： After being treated with 20 μmol/L, 40 μ/L, 80 μmol/L AG490 for 24, 48 and 72 h, the proliferation of MDA-MB-231 cells was inhibited in a dose-and time-dependent manner. MDA-MB-231 cells treated with 40 μmol/L AG490 for 30, 60, 90 and 120 rain resulted in the increasing adhesion of cells to Matrigel in a time-dependent manner. However, capacity of adhesion in the group treated with AG490 was significantly decreased in comparison with the control group （P〈0.01）. The expression level of P-ERK and MMP-9 were decreased when treated with AG490. After treatment with 40 μmol/L AG490, in invasion assay, the number of cells in AG490 treated group to migrate to filter coated with Matrigel was reduced compared with control group （P〈0.05） Meanwhile, in migration assay, the number of cells in AG490 treated group to migrate to filter was also decreased compared with control group （P〈0.05）. Conclusion： Our study indicates that JAK kinase could affect the activity of ERK signal transduction pathway through the phosphorylation of ERK. The inhibitory effects of JAK kinase on MMP-9 expression and invasion of breast cancer cells were associated with the down-regulation of the ERK signaling pathway.
Objective： To explore the effects of Janus activated kinase （JAK） inhibitor AG490 on the phosphorylation of extracellular signal regulated protein kinase （ERK） in human breast cancer cells MDA-MB-231 and the roles of JAK in the invasion and metastasis of the human breast cancer cells through ERK signaling transduction pathways. Methods： MDA-MB-231 cells were treated with 20 μmol/L, 40 μmol/L, 80 μmol/L Janus kinase inhibitor AG490 for 24, 48 and 72 h. Proliferation and adhesion of MDA-MB-231 cells to matrigel were measured with MTT assay. When treated with 40 μmol/L AG490 for 24 h, the expressions of P-ERK and MMP-9 of cells were detected by Western-blot and invasion and metastasis of MDA-MB-231 cells were evaluated with transwell chamber. Results： After being treated with 20 μmol/L, 40 μ/L, 80 μmol/L AG490 for 24, 48 and 72 h, the proliferation of MDA-MB-231 cells was inhibited in a dose-and time-dependent manner. MDA-MB-231 cells treated with 40 μmol/L AG490 for 30, 60, 90 and 120 rain resulted in the increasing adhesion of cells to Matrigel in a time-dependent manner. However, capacity of adhesion in the group treated with AG490 was significantly decreased in comparison with the control group （P〈0.01）. The expression level of P-ERK and MMP-9 were decreased when treated with AG490. After treatment with 40 μmol/L AG490, in invasion assay, the number of cells in AG490 treated group to migrate to filter coated with Matrigel was reduced compared with control group （P〈0.05） Meanwhile, in migration assay, the number of cells in AG490 treated group to migrate to filter was also decreased compared with control group （P〈0.05）. Conclusion： Our study indicates that JAK kinase could affect the activity of ERK signal transduction pathway through the phosphorylation of ERK. The inhibitory effects of JAK kinase on MMP-9 expression and invasion of breast cancer cells were associated with the down-regulation of the ERK signaling pathway.
基金
supported by the Scientific Research Foundation of Chonging Medical University (No. XBYB2007089).
