Degasperi Giovanna R, Zecchin Karina G, Borecký Jiri, Cruz-Höfling Maria A, Castilho Roger F, Velloso Lício A, Guimarães Fernando, Vercesi Anibal E
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-970, Brazil.
Eur J Pharmacol. 2006 Nov 7;549(1-3):179-84. doi: 10.1016/j.ejphar.2006.08.027. Epub 2006 Aug 26.
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.
最近，我们证明了维拉帕米（一种L型钙通道阻滞剂）可抑制成年大鼠Walker 256腹水瘤发展过程中脾淋巴细胞的激活。在本研究中，我们分析了荷Walker 256肿瘤大鼠的脾脏大小、脾淋巴细胞增殖、白髓组织及相对大小、食物摄入量以及血红蛋白水平的变化。这些大鼠出现脾脏肿大，同时白髓面积和TCD8 +淋巴细胞增殖显著增加。荷瘤大鼠体内γ干扰素水平升高，但白细胞介素-10水平未升高，表明存在Th1型免疫反应。这些表现伴随着食物摄入量减少和贫血。用维拉帕米治疗荷瘤大鼠可避免脾脏肿大，并增加细胞因子的表达以及脾TCD8 +淋巴细胞增殖。此外，维拉帕米治疗加剧了Walker肿瘤发展引起的厌食和贫血。在用维拉帕米治疗的对照大鼠中未观察到此类效应。综上所述，这些发现表明维拉帕米抑制对癌症的免疫反应，导致Walker 256肿瘤诱导的全身效应增加。
