Effects of lovastatin alone or combined with irradiation on tumor cells in vitro and in vivo.
OBJECTIVE
To evaluate the effect of lovastatin alone or combined with radiation on U87MG and FaDu cells in vitro and U87MG tumors in vivo.


METHODS
Cell number, p21(WAF1) expression, apoptosis, reproductive cell death, and cell-cycle distribution were investigated after incubation of U87MG and FaDu cells in vitro. The effect of lovastatin (50 mg/kg/day) on tumor growth and on tumor growth delay after single-dose irradiation with 20 Gy was investigated using U87MG tumors in nude mice.


RESULTS
Lovastatin dose dependently decreased cell number and proliferation of U87MG and FaDu cells. The proportion of cells in G0/G1 phase, apoptosis and p21 protein expression increased after lovastatin alone or combined with 4-Gy irradiation in both cell lines. Effects of lovastatin on cell cycle and cell number were more pronounced in U87MG compared to FaDu. No radiosensitization of clonogenic cells by lovastatin could be demonstrated in both cells lines, but the colony-forming ability after lovastatin alone was decreased in FaDu cells. In vivo, lovastatin decreased tumor volume over time but did not increase growth delay after irradiation of U87MG tumors with 20 Gy.


CONCLUSIONS
The data support effects of lovastatin on proliferation, apoptosis and colony-forming ability in vitro and tumor volume in vivo. At the drug concentration achievable, lovastatin did not improve the effects of radiation on U87MG tumors in vivo.
Gabryś
Dorota
D
Department of Radiation Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Dörfler
Annegret
A
Yaromina
Ala
A
Hessel
Franziska
F
Krause
Mechthild
M
Oertel
Reinhard
R
Baumann
Michael
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000473:pathology; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology; D066298:In Vitro Techniques; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*; D014410:Tumor Stem Cell Assay
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008148:Lovastatin