Blockers of Nicotinic Acetylcholine Receptors Delay Tumor Growth and Increase Antitumor Activity of Mouse Splenocytes.

Blockade of α6, α3ß2, α9α10, and α7 subtypes of nicotinic acetylcholine receptors slows tumor growth in vivo, increases cytotoxic activity of splenocytes from tumor-bearing mice, and, to some extent, reduces the viability of Ehrlich carcinoma cells in vitro. These data indicate that nicotinic acetylcholine receptors are involved in oncogenesis, affecting the survival of tumor cells, inter alia, via modulation of the antitumor immunity.

Suppression of Ehrlich carcinoma growth by cobra venom factor.

Cobra venom factor (CVF) depletes the complement system of the blood by forming stable convertase C3/C5 of the alternative pathway. We found that CVF from the Thailand cobra venom slows down the growth of subcutaneous Ehrlich carcinoma (EC) in mice at a dose of 1.7 nmol/g. Previously, we described a similar effect for the nerve growth factor (NGF) from the venom of this cobra. However, these factors did not exhibit either synergy or additive effect. On the contrary, they neutralized the antitumor effect of each other when they were administered simultaneously. Therefore, on the one hand, the NGF antitumor effect against EC manifests itself under the conditions of inflammation, and normal functioning of the complement system is necessary for this effect to occur. On the other hand, suppression of the humoral immune system leads to a slowdown of the EC growth, but administration of NGF prevents this.

α-conotoxins revealed different roles of nicotinic cholinergic receptor subtypes in oncogenesis of Ehrlich tumor and in the associated inflammation.

Multiple injections of conotoxin MII, a blocker of alfa3-ß2 and alfa6-containing subtypes of nicotinic acetylcholine receptors (n-AChRs), as well as conotoxin ArIB11L16D, a blocker of alfa7 subtype n-AChR, at a dose of 1 nmol/kg reduce both the lactate dehydrogenase level in tumor cells and the inflammatory leukocyte infiltration in tumor tissue in mice bearing Ehrlich carcinoma. The first stage of pathomorphism was detected in the tumor tissue after the treatment with the ArIB11L16D conotoxin, whereas the second stage was observed after the treatment with conotoxins RgIA and MII. Only MII injections led to a significant reduction in tumor growth. Our results show the involvement of n-AChRs in the regulation of metabolic processes and cell-cell interactions related to carcinogenesis and tumor-associated inflammation.

Dynamics of antitumor resistance after cyclophosphamide injection.

Antitumor resistance decreased in mice 24 h after injection of cyclophosphamide in a dose of 100 mg/kg. This was seen from more rapid growth of Ehrlich's ascitic carcinoma transplanted intraperitoneally 24 h after cyclophosphamide injection and 17% reduction of the lifespan of mice with tumors. Three, 7, 10, 14, and 22 days after cyclophosphamide injection, the antitumor resistance increased and the lifespan of animals with Ehrlich's ascitic carcinoma transplanted at the corresponding periods increased by 20, 14, 42, 29, and 36%, respectively, in comparison with mice with transplanted tumor not injected with the drug. Injection of cyclophosphamide 1 day after tumor transplantation prolonged of the lifespan of animals with tumors by 76%.