This study was conducted to investigate the modulatory effects of recombinant human tumor necrosis factor (rH‐TNF) and recombinant human interferon (rH‐IFN)‐α, ‐β and ‐γ, either alone or in combination, on the cytotoxicity of cisplatin, using MTT assay, against MKN‐45 (human stomach adenocarcinoma). MKN‐45 was resistant to rH‐TNF even at doses up to 103 U/ml. rH‐IFN‐γ inhibited the survival of MKN‐45 dose‐dependently, while rH‐IFN‐α and ‐β did not inhibit the survival of MKN‐45 even at the highest concentrations tested (104 U/ml). Combination of rH‐TNF with rH‐IFN‐α, ‐β or ‐γ did not significantly inhibit the survival of MKN‐45, except for a combination of 10 U/ral of rH‐TNF and 103 U/ml of rH‐IFN‐γ (P<0.05). Cisplatin inhibited the survival of MKN‐45 dose‐dependently. By the simultaneous combination of cisplatin with rH‐TNF and/or rH‐IFN‐α, ‐β or γ, cytotoxicity of cisplatin was enhanced and the combination effects were additive. The effects of rH‐TNF and rH‐IFN‐α, β and ‐γ on the modification of cytotoxicity of cisplatin were evaluated in terms of modification index (MI), demonstrating that rH‐TNF, rH‐IFN‐α, ‐β and ‐γ all augmented the cytotoxicity of cisplatin: MI values at 103 U/ml of rH‐IFN‐α, ‐β and ‐γ were 1.4, 1.4 and 2.3, respectively; those at the same concentrations of rH‐IFN‐α, ‐β and ‐γ in the presence of 10 U/ml of rH‐TNF were 3.6, 2.5 and 5.1, respectively. These results demonstrating that the cytotoxicity of cisplatin was enhanced by rH‐TNF and/or rH‐IFN‐α, ‐β or ‐γ suggest that cancer may be more effectively treated with the combination of cisplatin with these biological response modifiers than with cisplatin alone.
The effects of the agents that are related to intracellular events on interferon-gamma-induced class II major histocompatibility complex antigen expression were studied using the technique of immunocytochemistry. Rat class II major histocompatibility complex antigen (RT1.B) was expressed in 88.3 +/- 3.3% (n = 3) of the functioning rat thyroid cells (FRTL-5) cultured in a medium containing 100 U/ml recombinant rat interferon-gamma (IFN gamma). Deprivation of bovine TSH had no effect on the expression of RT1.B antigen by IFN gamma. A23187 (1 nM to 2 microM) and/or 10 nM to 10 microM phorbol 12-myristate 13-acetate did not induce the expression of RT1.B antigen. IFN gamma-induced RT1.B expression was not inhibited by either 10 nM to 100 microM 1-(5-isoquinolysulfonyl)-2-methylpiperazine or 200 nM to 200 microM 8-(N,N-dimethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride. It was also not inhibited by either 5-200 microM verapamil or 500 nM to 20 microM trifluoperazine. However, 0.01-10 micrograms/ml cycloheximide inhibited IFN gamma-induced RT1.B antigen expression in a dose-dependent manner. These results suggest that IFN gamma induces RT1.B antigen expression in FRTL-5 cells via de novo protein synthesis independent of the cAMP system, phosphatidylinositide system, and voltage-dependent calcium channel.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.