Imatinib interferes with survival of multi drug resistant Kaposi's sarcoma cells.
Multi drug resistance (MDR) is defined as the ability of tumor cells to become resistant to unrelated drugs. Tyrosine kinase inhibitor imatinib has been demonstrated to be effective in the treatment of certain tumors. In particular, imatinib inhibits Bcr-Abl kinase activity, c-kit and the phosphorylation of platelet-derived growth factor (PDGF) receptors. In this work, we show that imatinib inhibits PDGF phosphorylation not only in wt Kaposi sarcoma (KS) but also in multi drug resistant KS cells. This was associated with an increased apoptosis in wt cells and an increased autophagy in MDR-KS cells. These data add new insights to the possible use of imatinib in the overcoming of MDR in KS cells.
Cardiovascular Research Unit, Department of Medical Science, IRCCS San Raffaele, Rome, Italy.
Sabrina
S
Basciani
Rosa
R
Vona
Paola
P
Matarrese
Barbara
B
Ascione
Stefania
S
Mariani
Roberto
R
Cauda
Lucio
L
Gnessi
Walter
W
Malorni
Elisabetta
E
Straface
Mothanje Barbara
MB
Lucia
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000201:enzymology / Q000473:pathology*; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; D020169:Caspases