Summary
Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of Δ7-PGA was most marked, followed by that of Δ12-PGJ2, PGJ2 and PGD2. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ2 and Δ12-PGJ2 alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with Δ12-PGJ2, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD2 or Δ7-PGJ1, compared to the results in groups treated with PGD2 alone, Δ7-PGJ1 alone or cisplatin alone. Combination of PGJ2 or Δ12-PGJ2 and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD2 or Δ7-PGJ1 with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin.
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Abbreviations
- Cisplatin:
-
cis-diamminedichloro-platinum(II)
References
Bregman MD, Meyskens FL Jr (1983) In vitro modulation of human and murine melanoma growth by prostanoid analogues. Prostaglandins 26:449–456
Bregman MD, Funk, C, Fukushima M (1986) Inhibition of human melanoma growth by prostaglandin A, D, and J analogues. Cancer Res 46:2740–2744
Eisenbarth GS, Wellman DK, Leibovitz HE (1974) PGA1 inhibition of chondrosarcoma growth. Biochem Biophys Res Commun 60:1302–1308
Fukushima M Kato T, Ueda R, Ota K, Narumiya S, Hayaishi O (1982a) Prostaglandin D2, a potential antineoplastic agent. Biochem Biophys Res Commun 105:956–964
Fukushima M, Kato T, Ota K, Arai Y, Narumiya S, Hayaishi O (1982b) 9-Deoxy-delta9-prostaglandin D2, a prostaglandin D2 derivative with potent antineoplastic and weak smooth muscle contracting activities. Biochem Biophys Res Commun 109:626–633
Honn KV, Dunn JR, Morgan LR, Bienkowski M, Marnett LJ (1979) Inhibition of DNA synthesis in Harding-Passey melanoma cells by prostaglandins A1 and A2: comparison with chemotherapeutic agents. Biochem Biophys Res Commun 87:795–801
Kato T, Fukushima M, Kurozumi S, Noyori R (1986) Antitumor activity of Δ7-prostaglandin A1, and Δ12-prostaglandin J2 in vitro and in vivo. Cancer Res 46:3538–3542
Kawamura M, Koshihara Y (1983) Prostaglandin D2 strongly inhibits growth of murine mastocytoma cells. Prostaglandins Leukotrienes med 12:85–93
Kikuchi Y, Miyauchi M, Oomori K, Kita T, Kizawa I, Kato K (1986) Inhibition of human ovarian cancer cell growth in vitro and in nude mice by prostaglandin D2. Cancer Res 46:3364–3366
Kikuchi Y, Miyauchi M, Iwano I, Kita T, Oomori K, Kizawa I (1988) Adjuvant effects of prostaglandin D2 to cisplatin on human ovarian cancer cell growth in nude mice. Eur J Cancer Clin Oncol 24:1829–1833
Lane M (1979) Clinical problem of resistance to cancer chemotherapeutic agents. Fed Proc 38:103–107
Narumiya S, Fukushima M (1985) Delta12-prostaglandin J2, an ultimate metabolite of prostaglandin D2 exerting cell growth inhibition. Biochem Biophys Res Commun 127:739–745
Sakai T, Yamaguchi N, Shirosko Y, Sekiguchi M, Fujii G, Nishino H (1984) Prostaglandin D2 inhibits the proliferation of human malignant tumor cells. Prostaglandins 27:17–27
Santoro MG, Philpott GW, Jaffe BM (1976) Inhibition of tumor growth in vivo and in vitro by prostaglandin E. Nature 263:777–779
Sasaki H, Takada K, Terashima Y, Ekimoto H, Takahashi K, Tsuruo T, Fukushima M (1991) Human ovarian cancer cell lines resistant to cisplatin, doxorubicine andl-phenylalanine mustard are sensitive to Δ12-prostaglandin A1 and Δ12-prostaglandin J2. Gynecol Oncol 41:36–40
Simmet T, Jaffe BM (1983) Inhibition of B-16 melanoma growth in vitro by prostaglandin D2. Prostaglandins 25:47–54
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This work was supported in part by a grant-in-aid for comprehensive ten year strategy for cancer control from the Ministry of Health and Welfare of Japan (Y.K. and M.F.)
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Kikuchi, Y., Kita, T., Miyauchi, M. et al. Adjuvant effects of antineoplastic prostaglandins to cisplatin in nude mice bearing human ovarian cancer cells. J Cancer Res Clin Oncol 118, 453–457 (1992). https://doi.org/10.1007/BF01629429
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DOI: https://doi.org/10.1007/BF01629429