Verapamil-sensitive Ca2+ channel regulation of Th1-type proliferation of splenic lymphocytes induced by Walker 256 tumor development in rats.
Recently, we demonstrated that verapamil, an L-type Ca2+ channel blocker, inhibits the activation of splenic lymphocytes during Walker 256 ascitic tumor development in adult rats. In the present study we have analyzed the changes in spleen size, splenic lymphocyte proliferation, white pulp organization and relative size as well as food intake, and levels of blood haemoglobin in Walker 256 tumor bearing rats. These rats displayed a spleen enlargement associated with a significant increase in white pulp area and TCD8+ lymphocyte proliferation. Levels of interferon-gamma, but not of interleukin-10, were elevated in tumor bearing rats, indicating a Th1-type immune response. These manifestations were accompanied by reduced food intake and anaemia. Treatment of tumor bearing rats with verapamil avoided spleen enlargement and increased expression of cytokines, as well as the splenic TCD8+ lymphocyte proliferation. In addition, verapamil treatment promoted an exacerbation of the anorexia and anaemia caused by Walker tumor development. No such effect was observed in control rats treated with verapamil. Taken together, these findings suggest that verapamil inhibits the immune response to cancer, resulting in an increase of the systemic effects induced by Walker 256 tumor.
Degasperi
Giovanna R
GR
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-970, Brazil.
Zecchin
Karina G
KG
Borecký
Jiri
J
Cruz-Höfling
Maria A
MA
Castilho
Roger F
RF
Velloso
Lício A
LA
Guimarães
Fernando
F
Vercesi
Anibal E
AE
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006454:Hemoglobins; D016753:Interleukin-10; D007371:Interferon-gamma; D014700:Verapamil