Lovastatin and tumor necrosis factor-α exhibit potentiated antitumor effects against Ha-ras-transformed murine tumor via inhibition of tumor- induced angiogenesis

Wojciech Feleszko, Ewa Z. BaŁkowiec, Elisabeth Sieberth, Maria Marczak, Anna Dabrowska, Adam Giermasz, Anna Czajka, Marek Jakóbisiak

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)560-567
Number of pages8
JournalInternational Journal of Cancer
Volume81
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Lovastatin
Tumor Necrosis Factor-alpha
ras Genes
Neoplasms
Vascular Endothelial Growth Factor A
Vascular Tissue Neoplasms
ras Proteins
3T3 Cells
Hypercholesterolemia
Doxorubicin
Cisplatin
Blood Vessels
Melanoma
Growth
Pharmaceutical Preparations

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 journalArticle

Feleszko, Wojciech ; BaŁkowiec, Ewa Z. ; Sieberth, Elisabeth ; Marczak, Maria ; Dabrowska, Anna ; Giermasz, Adam ; Czajka, Anna ; Jakóbisiak, Marek. / Lovastatin and tumor necrosis factor-α exhibit potentiated antitumor effects against Ha-ras-transformed murine tumor via inhibition of tumor- induced angiogenesis. In: International Journal of Cancer. 1999 ; Vol. 81, No. 4. pp. 560-567.
@article{7f7f77ea00464d4b8daabda59feda15b,
title = "Lovastatin and tumor necrosis factor-α exhibit potentiated antitumor effects against Ha-ras-transformed murine tumor via inhibition of tumor- induced angiogenesis",
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.",
author = "Wojciech Feleszko and BaŁkowiec, {Ewa Z.} and Elisabeth Sieberth and Maria Marczak and Anna Dabrowska and Adam Giermasz and Anna Czajka and Marek Jak{\'o}bisiak",
year = "1999",
doi = "10.1002/(SICI)1097-0215(19990517)81:4<560::AID-IJC10>3.0.CO;2-7",
language = "English (US)",
volume = "81",
pages = "560--567",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

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 -