An in vitro study, evaluating the effect of sunitinib and/or lapatinib on two glioma cell lines.
OBJECTIVE
We sought to assess the effect of sunitinib and lapatinib applied either alone or in combination, on U87 and M059K glioma cells.


METHODS
Both cell lines were cultured as recommended by the manufacturer. Sunitinib and lapatinib were applied, either separately or in combination, in the cultured cells after cell attachment at doses of 10 nM, 100 nM, 1 microM and 10 microM. To determine whether the agents affect the proliferation of glioma cells, the 3-[4,5-dimethylthiazol-2-yl]-2,5 dimethyltetrazolium bromide assay was used. Apoptosis was detected using annexin V/propidium iodide detection assay, migration assay was performed in 24-well microchemotaxis chambers. The release of MMPs into the culture medium of U87 and M059K cells was measured by zymography.


RESULTS
Both agents, administered either alone or in combination, decreased cell proliferation in a dose-dependent manner 48 h after their application in both cell lines. The inhibition of their combination was statistically different than the inhibition of each agent alone. Apoptosis was increased and migration of U87 and M059K cells was inhibited either by each agent alone or their combination. MMPs levels remained unaffected by the application of both agents in U87 cells. However, MMP-9 and MMP-2 levels were decreased 48 h after treatment of M059K cells with sunitinib either alone or in combination with lapatinib.


CONCLUSIONS
Sunitinib and/or lapatinib appear to exhibit significant effects on proliferation, apoptosis and migration of glioma cells. When applied alone, sunitinib appears to be a more potent inhibitor than lapatinib.
Giannopoulou
Efstathia
E
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University Hospital of Patras, Patras Medical School, Rion, 26504, Greece.
Dimitropoulos
Konstantinos
K
Argyriou
Andreas A
AA
Koutras
Angelos K
AK
Dimitrakopoulos
Fotinos
F
Kalofonos
Haralabos P
HP
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077341:Lapatinib; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D011799:Quinazolines; D000077341:Lapatinib; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077210:Sunitinib