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Mitoxantrone inhibits growth of melanoma by increasing expression of calreticulin
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Abstract:
Objective:To investigate the effect of mitoxantrone (MIT) on calreticulin (CRT) expression in B16 cells, and to observe the immune effect of B16membrane antigen vaccine highly expressing CRT on B16 tumorbearing mice. Methods:The expression of CRT on membrane of B16 cells was detected by immunofluorescence after treatment with different concentrations of MIT. B16implanted mouse model was established, and the growth of B16implanted tumors and CRT expression in B16implanted tumor tissues were observed after treatment with different concentrations of MIT. Membrane antigen vaccines from both normal B16 cells and MITtreated B16 cells were prepared, and mice were immunized before B16 cell implantation. The infiltration of immune cells into B16 tumor tissues and the ratios of CD4+ and CD8+ T cells in the spleen of B16 tumorbearing mice were examined by immunohistochemistry and flow cytometry, respectively. Results:Flow cytometry results showed that MIT dosedependently increased CRT expression on B16 cell membrane, with CRT expression in control and high dosage MIT groups being (29.40±3.57)% and (72.20±2.94)% (P<0.05), respectively. MIT also increased CRT expression in B16 tumor tissues, with those in the control and high dosage MIT groups being 3.21±1.37 and 9.17±1.06 (P<0.05), respectively. MIT effectively inhibited the growth of B16 tumors (P<0.05). Compared with normal B16 cell membrane antigen vaccine, the vaccine highly expressing CRT increased the numbers of DCs and T cells in B16 tumors tissues and the ratios of CD4+ and CD8+ T cells in the spleen (P<0.05). Conclusion:MIT can increase CRT expression on membrane of B16 cells. B16membrane antigen vaccine highly expressing CRT can enhance the infiltration of DCs and T cells in melanoma, thus improving the immune effect of B16membrane antigen vaccine.
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Project Supported:
Project supported by the Science and Technology Research and Development Program of Hebei Province (No.09276418D26), and the Medical Practical Technology Program of Hebei Province (No.GL200928)
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