Abstract
Introduction: Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. Methods: To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. Results: After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p≤0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. Conclusion: These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability of cells.
Highlights
Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway
The results indicated that the protein expression of P53 in MCF7/ADM cell lines increased after RNA interference (RNAi) which means that Suppressors of cytokine signalling 1 (SOCS1) may participate in multidrug resistance (MDR) of breast cancer by regulating P53 expression (Figure 10)
These results indicated that SOCS1 may affect MDR-1 to inhibit P-gp expression in drug-resistant MCF7/ADM cell. (A) Expression of MDR1 mRNA in breast cancer cell line by Real Time-polymerase chain reaction (PCR); (B) Expression of MDR1 mRNA in breast cancer cell line by Western blot
Summary
Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. Recent improvements in early detection, surgical techniques and chemoradiotherapy have successfully advanced progressions in its treatment, its overall survival rate is still low.[3] Because of the significance of chemotherapy in treating breast cancer, the improvement of multidrug resistance (MDR) turns into a serious obstacle to successful chemotherapy.[4] In spite of the fact that the molecular mechanism(s) of the MDR have not yet been elucidated in breast cancer cells, a few studies have reported that the mechanisms of MDR were close connected with the overexpression of P-glycoprotein (P-gp) encoded by MDR1 gene in tumor cells.[5,6,7] the inhibition of P-gp expression in tumor cells could be a standout amongst the best approaches to reverse MDR and make tumor cells resensitize to chemotherapy.[8]
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