Mitoxantrone inhibits growth of melanoma by increasing expression of calreticulin / 中国肿瘤生物治疗杂志

ABSTRACT

Objective: To investigate the effect of mitoxantrone (MIT) on calreticulin (CRT) expression in B16 cells, and to observe the immune effect of B16-membrane antigen vaccine highly expressing CRT on B16 tumor-bearing mice. Methods: The expression of CRT on membrane of B16 cells was detected by immunofluorescence after treatment with different concentrations of MIT. B16-implanted mouse model was established, and the growth of B16-implanted tumors and CRT expression in B16-implanted tumor tissues were observed after treatment with different concentrations of MIT. Membrane antigen vaccines from both normal B16 cells and MIT-treated 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 tumor-bearing mice were examined by immunohistochemistry and flow cytometry, respectively. Results: Flow cytometry results showed that MIT dose-dependently 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. B16-membrane antigen vaccine highly expressing CRT can enhance the infiltration of DCs and T cells in melanoma, thus improving the immune effect of B16-membrane antigen vaccine.