Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of human cervical cancer

Levi S. Downs, Lisa M. Rogers, Yumi Yokoyama, Sundaram Ramakrishnan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective. To determine the impact of thalidomide and angiostatin on tumor growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer. Methods. Human umbilical endothelial cells were treated with angiostatin or thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and immunohistochemical analysis of tumors was used to determine degree of angiogenesis. TUNEL assay was used to assess apoptosis. Results. Angiostatin inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor growth by about 55%. We found no additive or synergistic effect when the two agents were combined. Both agents inhibited angiogenesis and induced apoptosis when compared to tumors from control animals. Conclusions. Angiostatin and thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this xenograft model of cervical cancer.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalGynecologic Oncology
Volume98
Issue number2
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Angiostatins
Thalidomide
Heterografts
Uterine Cervical Neoplasms
Growth
Neoplasms
Apoptosis
Endothelial Cells
Umbilicus
In Situ Nick-End Labeling
Nude Mice
Cell Proliferation

Keywords

  • Angiogenesis
  • Angiostatin
  • Cervical cancer
  • Thalidomide
  • Xenograft mouse model

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of human cervical cancer. / Downs, Levi S.; Rogers, Lisa M.; Yokoyama, Yumi; Ramakrishnan, Sundaram.

In: Gynecologic Oncology, Vol. 98, No. 2, 01.08.2005, p. 203-210.

Research output: Contribution to journalArticle

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AU - Rogers, Lisa M.

AU - Yokoyama, Yumi

AU - Ramakrishnan, Sundaram

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N2 - Objective. To determine the impact of thalidomide and angiostatin on tumor growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer. Methods. Human umbilical endothelial cells were treated with angiostatin or thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and immunohistochemical analysis of tumors was used to determine degree of angiogenesis. TUNEL assay was used to assess apoptosis. Results. Angiostatin inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor growth by about 55%. We found no additive or synergistic effect when the two agents were combined. Both agents inhibited angiogenesis and induced apoptosis when compared to tumors from control animals. Conclusions. Angiostatin and thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this xenograft model of cervical cancer.

AB - Objective. To determine the impact of thalidomide and angiostatin on tumor growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer. Methods. Human umbilical endothelial cells were treated with angiostatin or thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and immunohistochemical analysis of tumors was used to determine degree of angiogenesis. TUNEL assay was used to assess apoptosis. Results. Angiostatin inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor growth by about 55%. We found no additive or synergistic effect when the two agents were combined. Both agents inhibited angiogenesis and induced apoptosis when compared to tumors from control animals. Conclusions. Angiostatin and thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this xenograft model of cervical cancer.

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KW - Cervical cancer

KW - Thalidomide

KW - Xenograft mouse model

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