ABSTRACT
OBJECTIVE@#To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.@*METHODS@#Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot.@*RESULTS@#The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.@*CONCLUSION@#Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.
Subject(s)
Animals , Humans , Mice , Apoptosis , Drug Resistance, Neoplasm , Imatinib Mesylate/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Signal TransductionABSTRACT
Objective To explore the application of erlotinib based targeting fluorescent probe in the detection of lung cancer.Methods The erlotinib based targeting fluorescent probe was prepared.The lung cancer cells of A-549 were selected as experimental group,and cervical cancer cells of CaSki,SiHa and C33-A were selected as control group.The A-549,CaSki,SiHa and C33-A cells were identified by 0.1 × 10-6,1 × 10-6,10 × 10-6 mol · L-1 fluorescent probe;the identification ability of erlotinib based targeting fluorescent probe on cells in the two groups was observed under the inverted fluorescence microscope.Results When the concentration of fluorescent probe was 10 × 10-6 mol · L-1,the strong fluorescence signal was observed in A-549 and CaSki cells,but the fluorescence signal was not observed almost in SiHa and C33-A cells.When the concentration of fluorescent probe was 1 × 10-6 mol · L-1,the strong fluorescence signal was observed in A-549 cells;the weak fluorescence signal was observed in C33A cells;the fluorescence signal was not observed almost in SiHa and C33-A cells.When the concentration of fluorescent probe was 0.1 × 10-6 mol · L-1,the strong fluorescence signal was observed in A-549 cells;the fluorescence signal was not observed almost in CaSki,SiHa and C33-A cells.Conclusion Erlotinib based targeting fluorescent probe can specifically recognize lung cancer A-549 cells.