Antitumor effect of GnRH agonist in epithelial ovarian cancer

Jae-Hoon Kim, Dong Choon Park, Jin Woo Kim, Yang Kyu Choi, Young Ok Lew, Dae Hoon Kim, Jae Keun Jung, Young Ae Lim, Sung Eun Namkoong

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Abstract

Objective. The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp 6 ) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent. Methods. We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo. Results. Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6% compared with control, 4-5%. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy. Conclusions. Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.

Original languageEnglish
Pages (from-to)170-180
Number of pages11
JournalGynecologic Oncology
Volume74
Issue number2
DOIs
Publication statusPublished - 1999 Jan 1

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Gonadotropin-Releasing Hormone
DNA Nucleotidylexotransferase
Cell Line
Heterografts
Apoptosis
Severe Combined Immunodeficiency
Cultured Cells
Cell Cycle Resting Phase
Cell Cycle
Telomerase
Enzyme-Linked Immunosorbent Assay
G1 Phase
Cytostatic Agents
Ovarian Neoplasms
Ovarian epithelial cancer
CDC2 Protein Kinase
G2 Phase
Growth
Cell Division
Antineoplastic Agents

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

Cite this

Kim, J-H., Park, D. C., Kim, J. W., Choi, Y. K., Lew, Y. O., Kim, D. H., ... Namkoong, S. E. (1999). Antitumor effect of GnRH agonist in epithelial ovarian cancer. Gynecologic Oncology, 74(2), 170-180. https://doi.org/10.1006/gyno.1999.5413
Kim, Jae-Hoon ; Park, Dong Choon ; Kim, Jin Woo ; Choi, Yang Kyu ; Lew, Young Ok ; Kim, Dae Hoon ; Jung, Jae Keun ; Lim, Young Ae ; Namkoong, Sung Eun. / Antitumor effect of GnRH agonist in epithelial ovarian cancer. In: Gynecologic Oncology. 1999 ; Vol. 74, No. 2. pp. 170-180.
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abstract = "Objective. The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp 6 ) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent. Methods. We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo. Results. Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6{\%} compared with control, 4-5{\%}. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy. Conclusions. Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.",
author = "Jae-Hoon Kim and Park, {Dong Choon} and Kim, {Jin Woo} and Choi, {Yang Kyu} and Lew, {Young Ok} and Kim, {Dae Hoon} and Jung, {Jae Keun} and Lim, {Young Ae} and Namkoong, {Sung Eun}",
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Kim, J-H, Park, DC, Kim, JW, Choi, YK, Lew, YO, Kim, DH, Jung, JK, Lim, YA & Namkoong, SE 1999, 'Antitumor effect of GnRH agonist in epithelial ovarian cancer', Gynecologic Oncology, vol. 74, no. 2, pp. 170-180. https://doi.org/10.1006/gyno.1999.5413

Antitumor effect of GnRH agonist in epithelial ovarian cancer. / Kim, Jae-Hoon; Park, Dong Choon; Kim, Jin Woo; Choi, Yang Kyu; Lew, Young Ok; Kim, Dae Hoon; Jung, Jae Keun; Lim, Young Ae; Namkoong, Sung Eun.

In: Gynecologic Oncology, Vol. 74, No. 2, 01.01.1999, p. 170-180.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antitumor effect of GnRH agonist in epithelial ovarian cancer

AU - Kim, Jae-Hoon

AU - Park, Dong Choon

AU - Kim, Jin Woo

AU - Choi, Yang Kyu

AU - Lew, Young Ok

AU - Kim, Dae Hoon

AU - Jung, Jae Keun

AU - Lim, Young Ae

AU - Namkoong, Sung Eun

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Objective. The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp 6 ) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent. Methods. We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo. Results. Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6% compared with control, 4-5%. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy. Conclusions. Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.

AB - Objective. The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp 6 ) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent. Methods. We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo. Results. Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6% compared with control, 4-5%. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy. Conclusions. Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.

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