Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tomors

Paul G Braunschweiger, Vathsala S. Basrur, Octavio Santos, Arnold Markoe, Pavel V. Houdek, James G. Schwade

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The antitumor activity of cis-diamminedichloroplatinum(II) (cP) and human recombinant interleukin-1α (IL-1α) was studied in RIF-1 and SC VII solid tumor models and in a cP-resistant subline of RIF-1 designated RIF-R1cP. In RIF-1 tumors, clonogenic cell survival after cP plus IL-1α combinations was highly schedule and IL-1α dose dependent. More than additive clonogenic cell kill was seen when cP was given 6 h before, but not 8 h before or at 2-6 h after IL-1α. Time course studies indicated that maximal clonogenic cell killing was achieved within 4-6 h after the cP plus IL-1α combination, with little or no recovery for up to 24 h. In vivo dose-response studies indicated that cP plus IL-1α combinations induced more clonogenic cell kill than cP alone in all three tumor models, and analysis by the median effect principle indicated highly synergistic antitumor activity. Dexamethasone but not indomethacin inhibited the synergistic interaction. IL-1α had no effect on the cytotoxicity of cP in SCC VII cells in vitro, and neither in vitro hypoxia nor in vivo ischemia, induced by clamping tumor blood supply, significantly affected cP clonogenic cell killing. Increased clonogenic cell killing was seen, however, after removal of the clamp, implicating reperfusion events, such as oxyradical stress, as a potential mechanism for increased cP cytotoxicity in SCC VII solid tumors. The data from our model systems provide a rationale for additional work to define the mechanisms of the synergistic antitumor activity of the cP plus IL-1α combination and indicate that IL-1α might be a useful adjunct to increase the clinical efficacy of cP-containing strategies for both sensitive and cP-resistant cancers.

Original languageEnglish
Pages (from-to)1091-1097
Number of pages7
JournalCancer Research
Volume53
Issue number5
StatePublished - Mar 1 1993

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Interleukin-1
Cisplatin
Neoplasms
Constriction
Indomethacin
Dexamethasone
Reperfusion
Cell Survival
Appointments and Schedules
Ischemia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Braunschweiger, P. G., Basrur, V. S., Santos, O., Markoe, A., Houdek, P. V., & Schwade, J. G. (1993). Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tomors. Cancer Research, 53(5), 1091-1097.

Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tomors. / Braunschweiger, Paul G; Basrur, Vathsala S.; Santos, Octavio; Markoe, Arnold; Houdek, Pavel V.; Schwade, James G.

In: Cancer Research, Vol. 53, No. 5, 01.03.1993, p. 1091-1097.

Research output: Contribution to journalArticle

Braunschweiger, PG, Basrur, VS, Santos, O, Markoe, A, Houdek, PV & Schwade, JG 1993, 'Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tomors', Cancer Research, vol. 53, no. 5, pp. 1091-1097.
Braunschweiger PG, Basrur VS, Santos O, Markoe A, Houdek PV, Schwade JG. Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tomors. Cancer Research. 1993 Mar 1;53(5):1091-1097.
Braunschweiger, Paul G ; Basrur, Vathsala S. ; Santos, Octavio ; Markoe, Arnold ; Houdek, Pavel V. ; Schwade, James G. / Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tomors. In: Cancer Research. 1993 ; Vol. 53, No. 5. pp. 1091-1097.
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