ABSTRACT
Objective To determine the association of high IL-1β levels with the migration of lung cancer H460 cells with acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods The resistant cells were referred to as H460-TR in this study. IL-1β levels in H460-TR cells and the parent H460 (H460-WT) cells were measured through RT-PCR, Western blot, and enzyme-linked immunosorbent assay. The migration capacity of the cells was determined using the migration transwell assay. The extent of migration and the activation of phosphatidyl-inositol 3-kinase/serine-threonine kinase (PI3K/Akt) were detected in H460 cells treated with or without human recombinant IL-1 or IL-1R antagonist. Results Migration capacity of H460-TR cells in the conditioned medium and its IL-1β level were higher than those of H460-WT cells . The migration capacity and Akt activation were consistent with the IL-1β level in lung cancer H460 cells. Conclusions Significantly elevated IL-1β expression in cancer cells is associated with the high migration capacity of H460-TR cells, and Akt activation. Akt signaling as the downstream pathway of IL-1β and IL-1βmay function as a therapeutic target for metastatic lung cancer.
ABSTRACT
Objective To investigate the effect of norepinephrine (NE) on the proliferation and migration capacity of endo‐thelial progenitor cells (EPCs) ,and bone marrow mobilization and to analyze its molecular mechanism .Methods The 8‐week old C57 mice were taken and randomly divided into 3 groups ,5 cases in each group :the blank control group(subcutaneous injection of normal saline without operaion) ,model group(subcutaneous injection of normal saline and ischemia in left lower extremity ) and NE group(subcutaneous injection of NE 100μmol/100 μL and ischemia in left lower extremity) .The limb ischemia model was prepared by adopting the femoral arterial ligation in mouse left lower extremity ,then NE was continuously pumped by the micro‐osmotic pump .The EPCs contents from bone marrow ,peripheral blood and spleen were assayed with the flow cytometric analyzer ;human peripheral blood EPCs were cultured and stimulated by NE .The proliferation and migration capacity ,and the activation situation of Akt and eNOS signal pathway were detected .Results NE could promote the mobilization of bone marrow EPCs in limb ischemia mice ,increased the EPCs quantity of peripheral blood and spleen ,comparing the NE group with the model group ,the EPCs quantity was increased for bone marrow [(3 .271 ± 0 .772)% vs .(1 .320 ± 0 .256)% ] ,peripheral circulation[(0 .261 ± 0 .041)% vs .(0 .110 ± 0 .028)% ] and spleen[(4 .671 ± 0 .345)% vs .(1 .880 ± 0 .0 .381)% ] ,the differences were statistically significant (P<0 .01) .NE could promote the proliferation and migration capacity ,moreover could activate the Akt‐eNOS signal pathway in EPCs with a dose dependent manner .Conclusion NE could promote the proliferation and migration of EPCs and mouse bone marrow mobilization via the Akt‐eNOS signal pathway .