Doxorubicin resistant neuroblastoma cells secrete factors that activate AKT and attenuate cytotoxicity in drug-sensitive cells.
The present study aims to verify the hypothesis that tumor cells with acquired resistance to chemotherapy may secrete survival factors and thus, participate in the protection of drug-sensitive cells against drug toxicity. A human neuroblastoma cell line, SK-N-SH, and its doxorubicin resistant derivative, RDOX6, have been used. Conditioned medium from RDOX6 cells attenuated the cytotoxic response of SK-N-SH cells to doxorubicin. This protective effect was associated with activation of the Akt survival pathway and inhibition of caspase-3. These data indicate that secretion, by drug-resistant cells, of factors that activate anti-apoptotic pathways in drug-sensitive cells, may constitute a novel mechanism of drug resistance.
Emran
Mohammad A
MA
Department of Surgery, Illinois Masonic Medical Center, Children's Memorial Institute for Education and Research (CMIER), Cancer Biology and Chemotherapy Program, Northwestern University Medical School, Chicago, IL 60614, USA.
Rebbaa
Abdelhadi
A
Mirkin
Bernard L
BL
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017077:Culture Media, Conditioned; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D017077:Culture Media, Conditioned; D011518:Proto-Oncogene Proteins; D004317:Doxorubicin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases