RESUMO
Recent studies have found that glucocorticoids are closely associated with oncogenesis and the development of many types of tumors. The aim of this study was to observe the effect of dexamethasone on the growth and angiogenesis of transplanted Lewis lung carcinoma in mice. Lewis lung carcinoma cells were inoculated subcutaneously into the right axilla of C57BL/6 mice, and the mice were randomly divided into 3 groups: the control group, cisplatin group, and dexamethasone group. From day 7 after inoculation, all the mice were given different treatments for 10 days, and changes in xenograft tumor volumes were monitored. All mice were sacrificed on day 17, and the tumors were obtained and weighed and the tumor inhibitory rate was calculated. The expression levels of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), as well as the microvessel density (MVD) in the tumor mass, were measured by immunohistochemistry. Tumor growth was suppressed in the cisplatin group and dexamethasone group. The weights of tumors were markedly decreased in the cisplatin group and dexamethasone group compared with the control group (P < 0.05). The expression levels of HIF-1α and VEGF and the MVD were significantly lower in the cisplatin group and dexamethasone group than in the control group (P < 0.05). However, these levels were not significantly different between the cisplatin group and dexamethasone group (P > 0.05). Dexamethasone can effectively inhibit the growth and angiogenesis of Lewis lung carcinoma by inhibiting the expression of HIF-1α and VEGF.
Assuntos
Carcinoma Pulmonar de Lewis/prevenção & controle , Dexametasona/farmacologia , Neovascularização Patológica/prevenção & controle , Carga Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/irrigação sanguínea , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Glucocorticoides/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Passive immunotherapy against soluble pro-angiogenic factors and/or their receptors in endothelial cells has become a promising approach in cancer therapeutics. There is also experimental evidence indicating that an active immunotherapy strategy directed towards these target molecules could also be effective. In this paper we show that it is possible to reduce tumor growth or increase the survival of tumor-bearing C57Bl/6 mice when animals are vaccinated with the human vascular endothelial growth factor (VEGF) isoform 121 gene (hVEGF(121)), and later challenged with melanoma or lung carcinoma tumor cells. Immunization was done with 10 microg DNA doses of the hVEGF121 gene, which is highly homologous to its mouse counterpart, administered on a weekly basis using a plasmid bearing 5 CpG bacterial motifs. Histopathology analyses of tumors of hVEGF(121) immunized animals showed a decrease in tumor cell density around vessels and in mitotic figures, as well as an increase in apoptotic tumor cells. A statistically significant cell cytotoxic response was found when spleen cells of immunized mice were co-cultured in vitro with mouse tumor VEGF-producing cells. Vaccination with an hVEGF121 gene mutated to make it deficient for VEGF receptor binding, produced similar in vitro and in vivo results, and significantly reduced the number of spontaneous metastases produced by the mouse Lewis lung carcinoma. Our results indicate that human VEGF DNA can be employed for anti-angiogenic active immunotherapy in mice, and that direct cell cytotoxicity is a contributor mechanism to the overall anti-tumor effects seen in immunized animals.