Abstract
This study aimed to investigate whether the biological response modifiers (BRM) interferon γ (IFNγ) and tumour necrosis factor α (TNFα) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFNγ was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNFα demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNFα and IFNγ demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.
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References
Aggarwal BB, Eussalu TE, Hass PE (1985) Characterisation of receptors for human TNF and their regulation by gamma-interferon. Nature 318: 665
Alexander RB, Nelson WG, Coffey DS (1987) Synergistic enhancement by tumor necrosis factor of in vitro cytotoxicity from chemotherapeutic drugs targeted at DNA topoisomerase II. Cancer Res 47: 2403
Annual report of the results of treatment of gynecological cancer (1990) Int J Gynecol Obstet 36 [Suppl]: 238
Balkwill FR, Lee A, Aldam G, Moodie E, Thomas A, Travernier J, Fiers W (1986) Human tumor xenografts treated with recombinant TNF alone or in combination with interferons. Cancer Res 46: 3990
Balkwill FR, Ward BG, Moodie E, Fiers W (1987) Therapeutic potential of TNF alpha and gamma interferon in experimental human ovarian cancer. Cancer Res 47: 4755
Beouckaert PGG, Leroux-Roels GG, Guisez Y, Taverner J, Fiers W (1986) In vivo anti-tumour activity of recombinart human and murine TNF, alone and in combination with murine IFN gamma. Int J Cancer 38: 763
Berenbaum MC (1981) Criteria for analyzing interactions between biologically active agents. Adv Cancer Res 35: 269
Billi G, Venturini M, Piccini D, Parodi S, Rosso R, Conte PF, Rosso P (1992) Synergistic cytotoxic effects of recombinant human TNF and etoposide or doxorubicin on A2774 human epithelial ovarian cancer cell line. Int J Gynecol Cancer 2: 147
Bonavida B, Tsuchitani T, Zighelboim J, Berek JS (1990) Synergy is doccumented in vitro with low dose recombinant TNF, cisplatin and doxorubicin in ovarian cancer cells. Gynecol Oncol 38: 333
Das AK, Walther PJ, Buckley NJ, Poulton SHM (1989) Recombinant human tumour necrosis factor alone and in combination with chemotherapeutic agents. Arch Surg 124: 107
Dealtry GB, Balkwill FR (1987) Cell growth inhibition by interferons and TNF In: Clemens MJ, Morris AG, Gearing AJH (eds) Lymphokines and interferons: a practical approach. IRL Press, Oxford
Fransen L, Heyden J van der, Ruysschaert R, Fiers W (1986) Recombinant TNF—its effect and its synergism with interferongamma on a variety of normal and transformed human cell lines. Eur J Cancer Clin Oncol 22: 419
Gresser I (1985) How does interferon inhibit tumor growth? In: Gresser I (ed) Interferon, vol. 6. Academic Press, New York, p 93
Hayward IP, Hurst T, Parsons PG, Khoo SK (1992) Combination chemotherapy tested in a short-term thymidine incorporation assay in primary cultures of ovarian adenocarcinomas. Int J Cell Cloning 10: 182
Khoo SK, Hurst T, Webb MJ, Mackay EV (1986) Short-term in vitro chemosensitivity testing of tumours of the ovary, cervix and uterus. Aust NZ J Obstet Gynaecol 26: 288
Langdon SP, Lawrie SS, Hay FG, Hawkes MM, McDonald A, Hayward IP, Schol DJ, Hilgers J, Leonard RCF, Smyth JF (1988) Characterization and properties of nine ovarian adenocarcinoma cell lines. Cancer Res 48: 6166
Old LJ (1985) Tumor necrosis factor. Science 230: 630
Ratliff TL, Kadmon D, Shapiro A, Jacobs AJ, Heston WDW (1984) Inhibition of mouse bladder tumor proliferation by murine interferon gamma and its synergism with interferon beta. Cancer Res 44: 4377
Saito T, Berens ME, Welander CE (1986) Direct and indirect effects of human recombinant interferon on tumor cells in a clonogenic assay. Cancer Res 46: 6413
Smyth MJ, Pieterz GA, McKenzie IFC (1988) Increased antitumour effect of immunoconjugates and tumour necrosis factor in vivo. Cancer Res 48: 3607
Stone-Wolff DS, Yip YK, Kelker HC, Junming LE, Henriksendestefano D, Rubin BY, Rinderknecht E, Aggarwal BB, Vilcek J (1984) Interrelationships of human interferon gamma with lymphotoxin and monocyte cytotoxin. J Exp Med 159: 828
Sugarman BJ, Aggarwal BB, Hass PE (1985) Recombinant tumour necrosis alpha: effects of proliferation on normal and transformed cell lines in vitro. Science 230: 943
Toy J (1983) The interferons. Clin Exp Immunol 54: 1
Van Haaften Day C, Russel P, Rugg C, Wills EJ, Tattersall MH (1983) Flow cytometric and morphological studies of ovarian carcinoma cell lines and xenografts. Cancer Res 43: 3725
Ward BG, Wallace K, Shepherd JH, Balkwill FR (1987) Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice. Cancer Res 47: 2662
Wilson AP (1984) Characterisation of a cell line derived from the ascites of a patient with papillary serous cystadenocarcinoma of the ovary. J Natl Cancer Inst 72: 513
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Clark, S., McGuckin, M.A., Hurst, T. et al. Effect of interferon γ and tumour necrosis factor α on sensitivity to cisplatin in ovarian carcinoma cell lines. Cancer Immunol Immunother 39, 100–104 (1994). https://doi.org/10.1007/BF01525315
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DOI: https://doi.org/10.1007/BF01525315