Anti-ENO1 antibody combined with metformin reverses the resistance of human non-small cell lung cancer A549 cells to cetuximab by targeting cancer stem cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation, migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX(35 µg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.

The discovery of antitumor compounds from marine sponge targeting lung cancer stem cells / 药学实践杂志

Objective To screen the active compounds targeting lung cancer stem cells (LCSCs) from the sponge Aaptos aaptos.Methods The A549-Nanog-GFP model of LCSCs was constructed.Western blot and immunofluorescence were used to examine the expression of pluripotency markers in screening model.The established LCSCs model was used to screen 8 fractions of Aaptos aaptos dichloromethane extract.The active fraction was separated by various chromatographic methods.CCK8 assay was used to screen the compounds for anti-LCSCs activity in vitro.Results LCSCs model with high expression of CD44 and ALDH1A1 protein was successfully constructed.The fraction D6 showed significant inhibitory activity in LCSCs(P<0.01).Four aaptamine alkaloids were isolated from this fraction.Compound AP-1 has good activity against LCSCs(P<0.01)with IC50 value(3.84±0.12) μmol/L.Conclusion AP-1 isolated from the spongeAaptos aaptos exhibited significant activity against LCSCs.