Endostatin gene therapy enhances the efficacy o IL-2 in suppressing metastatic renal cell carcinoma in mice
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Cancer Immunology Immunotherapy
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We investigated whether the administration of
IL-2 combined with endostatin gene therapy was able to
produce additive or even synergistic immunomodulatory
activity in a mouse model of metastatic renal carcinoma.
Renca cells were injected into the tail vein of BALB/c
mice. After 24 h, the animals were randomly divided into
four groups (5 mice/group). One group of mice was the
control, the second group received treatment with 100,000
UI of Recombinant IL-2 (Proleukin, Chiron) twice a day,
1 day per week during 2 weeks (IL-2), the third group
received treatment with a subcutaneous inoculation of
3.6 £ 106
endostatin-producing cells, and the fourth group
received both therapies (IL-2 + ES). Mice were treated for
2 weeks. In the survival studies, 10 mice/group daily, mice
were monitored daily until they died. The presence of
metastases led to a twofold increase in endostatin levels.
Subcutaneous inoculation of NIH/3T3-LendSN cells
resulted in a 2.75 and 2.78-fold increase in endostatin levels
in the ES and IL-2 + ES group, respectively. At the end of
the study, there was a signiWcant decrease in lung wet
weight, lung nodules area, and microvascular area (MVA)
in all treated groups compared with the control group
(P < 0.001). The signiWcant diVerence in lung wet weight
and lung nodules area between groups IL-2 and IL-2 + ES
revealed a synergistic antitumor eVect of the combined
treatment (P < 0.05). The IL-2 + ES therapy Kaplan–Meier
survival curves showed that the probability of survival was
signiWcantly higher for mice treated with the combined
therapy (log-rank test, P = 0.0028). Conjugated therapy
caused an increase in the inWltration of CD4, CD8 and
CD49b lymphocytes. An increase in the amount of CD8
cells (P < 0.01) was observed when animals received both
ES and IL-2, suggesting an additive eVect of ES over IL-2
treatment. A synergistic eVect of ES on the inWltration of
CD4 (P < 0.001) and CD49b cells (P < 0.01) was also
observed over the eVect of IL-2. Here, we show that ES led
to an increase in CD4 T helper cells as well as cytotoxic
lymphocytes, such as NK cells and CD8 cells, within
tumors of IL-2 treated mice. This means that ES plays a
role in supporting the actions of T cells.
Como referenciar
ROCHA, FLAVIA G. de G.; CHAVES, KAREN C.B.; CHAMMAS, ROGER; PERON, JEAN P.S.; RIZZO, LUIZ V.; SCHOR, NESTOR; BELLINI, MARIA H. Endostatin gene therapy enhances the efficacy o IL-2 in suppressing metastatic renal cell carcinoma in mice. Cancer Immunology Immunotherapy, v. 59, n. 9, p. 1357-1365, 2010. DOI: 10.1007/s00262-010-0865-6. Disponível em: http://repositorio.ipen.br/handle/123456789/8151. Acesso em: 20 Mar 2026.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.