Human growth hormone gene transfer into tumor cells may improve cancer chemotherapy.
Chemotherapy remains the main tool for the treatment of cancers, but is often hampered by tumor cell resistance. In this context, the transfer of genes able to accentuate the effect of anticancer drugs may constitute a useful approach, as exemplified by inactivation of nuclear factor (NF)-kappa B via direct transfer of a gene encoding a negative dominant of its natural inhibitor I kappa B, leading to improved response to cancer chemotherapy. Following our previous report that transfection of human growth hormone (hGH) gene into human monocytic cell lines may also inactivate NF-kappa B in another situation, we decided to test the consequences of hGH gene transfer on cancer treatments. We demonstrated that hGH-transfected human myeloid leukemia U937 cells were sensitized to an apoptotic signal mediated by the anticancer drugs. In parallel, we found that, by inhibiting degradation of I kappa B, hGH gene transfer diminished NF-kappa B entry into the nuclei of U937 cells exposed to daunorubicin. Finally, we report that hGH-transfected tumor cells engrafted in nude mice responded in vivo to chemotherapy with nontoxic doses of daunorubicin whereas, under the same conditions, control tumor cells remained insensitive. Overall, this study therefore suggests that hGH gene transfer may offer new therapeutic prospects in cancer therapy.
Cherbonnier
C
C
INSERM U542/Paris XI University, Villejuif Cider, France.
Déas
O
O
Vassal
G
G
Merlin
J L
JL
Haeffner
A
A
Senik
A
A
Charpentier
B
B
Dürrbach
A
A
Bénard
J
J
Hirsch
F
F
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D003131:Combined Modality Therapy; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D019382:Human Growth Hormone; D003630:Daunorubicin