PRIMA-1(MET) synergizes with cisplatin to induce tumor cell apoptosis.
Mutant p53-carrying tumors are often more resistant to chemotherapeutical drugs. We demonstrate here that the mutant p53-reactivating compound PRIMA-1(MET) acts synergistically with several chemotherapeutic drugs to inhibit tumor cell growth. Combined treatment with cisplatin and PRIMA-1(MET) resulted in a synergistic induction of tumor cell apoptosis and inhibition of human tumor xenograft growth in vivo in SCID mice. The induction of mutant p53 levels by chemotherapeutic drugs is likely to increase the sensitivity of tumor cells to PRIMA-1(MET). Thus, the combination of PRIMA-1(MET) with currently used chemotherapeutic drugs may represent a novel and more efficient therapeutic strategy for treatment of mutant p53-carrying tumors.
Bykov
Vladimir J N
VJ
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Stockholm, Sweden.
Zache
Nicole
N
Stridh
Helene
H
Westman
Jacob
J
Bergman
Jan
J
Selivanova
Galina
G
Wiman
Klas G
KG
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001372:Aza Compounds / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000473:pathology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D012516:Osteosarcoma / Q000473:pathology*; D011812:Quinuclidines / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011812:Quinuclidines; C451219:2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one; D002945:Cisplatin; C533410:eprenetapopt