Abstract
Lovastatin, a drug commonly used in the treatment of hypercholesterolemia, has previously been reported to exert potentiated antitumor activity when combined with either tumor necrosis factor-α (TNF- α), cisplatin or doxorubicin in a melanoma model in mice. Since lovastatin interferes with the function of ras oncogene-encoded (Ras) proteins, we have investigated the antitumor activity of lovastatin and TNF-α using a Ha-ras- transformed murine tumor model. In in vitro studies, lovastatin inhibited the growth of cells transformed with Ha-ras oncogene (Ras-3T3 and HBL100-ras cells) more effectively than control NIH-3T3 and HBL100-neo cells. In in vivo experiments, the Ras-3T3 tumor demonstrated significantly increased sensitivity to combined treatment with both lovastatin (50 mg/kg) and TNF-α (1 μg/day) compared with either agent alone. Combined treatment with both agents also resulted in greater inhibition of blood-vessel formation. Ras- 3T3 tumor cells produced increased amounts of vascular endothelial growth factor (VEGF) and lovastatin effectively suppressed VEGF production by these cells. Our results suggest that lovastatin increases antitumor activity of TNF-α against tumor cells transformed with v-Ha-ras oncogene via inhibition of tumor-induced blood-vessel formation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 560-567 |
| Number of pages | 8 |
| Journal | International Journal of Cancer |
| Volume | 81 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1999 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Cancer Research
Cite this
Lovastatin and tumor necrosis factor-α exhibit potentiated antitumor effects against Ha-ras-transformed murine tumor via inhibition of tumor- induced angiogenesis. / Feleszko, Wojciech; BaŁkowiec, Ewa Z.; Sieberth, Elisabeth; Marczak, Maria; Dabrowska, Anna; Giermasz, Adam; Czajka, Anna; Jakóbisiak, Marek.
In: International Journal of Cancer, Vol. 81, No. 4, 1999, p. 560-567.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lovastatin and tumor necrosis factor-α exhibit potentiated antitumor effects against Ha-ras-transformed murine tumor via inhibition of tumor- induced angiogenesis
AU - Feleszko, Wojciech
AU - BaŁkowiec, Ewa Z.
AU - Sieberth, Elisabeth
AU - Marczak, Maria
AU - Dabrowska, Anna
AU - Giermasz, Adam
AU - Czajka, Anna
AU - Jakóbisiak, Marek
PY - 1999
Y1 - 1999
N2 - Lovastatin, a drug commonly used in the treatment of hypercholesterolemia, has previously been reported to exert potentiated antitumor activity when combined with either tumor necrosis factor-α (TNF- α), cisplatin or doxorubicin in a melanoma model in mice. Since lovastatin interferes with the function of ras oncogene-encoded (Ras) proteins, we have investigated the antitumor activity of lovastatin and TNF-α using a Ha-ras- transformed murine tumor model. In in vitro studies, lovastatin inhibited the growth of cells transformed with Ha-ras oncogene (Ras-3T3 and HBL100-ras cells) more effectively than control NIH-3T3 and HBL100-neo cells. In in vivo experiments, the Ras-3T3 tumor demonstrated significantly increased sensitivity to combined treatment with both lovastatin (50 mg/kg) and TNF-α (1 μg/day) compared with either agent alone. Combined treatment with both agents also resulted in greater inhibition of blood-vessel formation. Ras- 3T3 tumor cells produced increased amounts of vascular endothelial growth factor (VEGF) and lovastatin effectively suppressed VEGF production by these cells. Our results suggest that lovastatin increases antitumor activity of TNF-α against tumor cells transformed with v-Ha-ras oncogene via inhibition of tumor-induced blood-vessel formation.
AB - Lovastatin, a drug commonly used in the treatment of hypercholesterolemia, has previously been reported to exert potentiated antitumor activity when combined with either tumor necrosis factor-α (TNF- α), cisplatin or doxorubicin in a melanoma model in mice. Since lovastatin interferes with the function of ras oncogene-encoded (Ras) proteins, we have investigated the antitumor activity of lovastatin and TNF-α using a Ha-ras- transformed murine tumor model. In in vitro studies, lovastatin inhibited the growth of cells transformed with Ha-ras oncogene (Ras-3T3 and HBL100-ras cells) more effectively than control NIH-3T3 and HBL100-neo cells. In in vivo experiments, the Ras-3T3 tumor demonstrated significantly increased sensitivity to combined treatment with both lovastatin (50 mg/kg) and TNF-α (1 μg/day) compared with either agent alone. Combined treatment with both agents also resulted in greater inhibition of blood-vessel formation. Ras- 3T3 tumor cells produced increased amounts of vascular endothelial growth factor (VEGF) and lovastatin effectively suppressed VEGF production by these cells. Our results suggest that lovastatin increases antitumor activity of TNF-α against tumor cells transformed with v-Ha-ras oncogene via inhibition of tumor-induced blood-vessel formation.
UR - http://www.scopus.com/inward/record.url?scp=0344948143&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344948143&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19990517)81:4<560::AID-IJC10>3.0.CO;2-7
DO - 10.1002/(SICI)1097-0215(19990517)81:4<560::AID-IJC10>3.0.CO;2-7
M3 - Article
C2 - 10225445
AN - SCOPUS:0344948143
VL - 81
SP - 560
EP - 567
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -