In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002)

Limin Hu, Charles Zaloudek, Gordon Mills, Joe Gray, Robert B. Jaffe

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

Phosphatidylinositol 3-kinase (PI3-K) induces mitogenesis, cell growth, and cell transformation. Amplification of the gene encoding the P110α subunit likely is an important event in ovarian cancer progression, and PI3-K inhibitors are possible therapeutic agents for this disease. We evaluated effects of LY294002, a potent inhibitor of PI3-K, on growth of ovarian carcinoma in vivo and in vitro, and on ascites formation in vivo. Athymic mice were inoculated i.p. with the ovarian cancer cell line OVCAR-3. Seven days after inoculation, mice were treated with or without LY294002 (100 mg/kg of body weight) for 3 weeks. Body weight and abdominal circumference were measured twice weekly. At the end of the experiment, mice were sacrificed, ascites volume was measured, and tumors were excised. Mean tumor burden in the LY294002-treated group was reduced by ~65% versus controls. Virtually no ascites developed in the treatment group; mean volume of ascites in controls was 3.3 ± 0.38 ml. OVCAR-3 cells also were cultured in vitro without and with LY294002 (1, 5, and 10 μM) for 24 h. The number of cells in 1, 5, and 10 μM LY294002-treated wells was reduced by 27, 56, and 75%, respectively, versus controls. In vivo and in vitro morphological studies demonstrated that LY294002 induced marked nuclear pyknosis and diminished cytoplasmic volume in the tumor cells, confirmed as apoptosis. Thus, LY294002 significantly inhibits growth and ascites formation of ovarian carcinoma in vivo and markedly inhibits ovarian cancer cell proliferation in vitro, suggesting an important role of PI3-K inhibitors as a potentially useful treatment for women with ovarian carcinoma.

Original languageEnglish (US)
Pages (from-to)880-886
Number of pages7
JournalClinical Cancer Research
Volume6
Issue number3
StatePublished - Mar 2000
Externally publishedYes

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Phosphatidylinositol 3-Kinase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Ascites
Carcinoma
Growth
Ovarian Neoplasms
Tumor Burden
Body Weight
Gene Amplification
In Vitro Techniques
Nude Mice
Therapeutics
Cell Count
Cell Proliferation
Apoptosis
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). / Hu, Limin; Zaloudek, Charles; Mills, Gordon; Gray, Joe; Jaffe, Robert B.

In: Clinical Cancer Research, Vol. 6, No. 3, 03.2000, p. 880-886.

Research output: Contribution to journalArticle

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