Effect Of Combined Pimozide And CpG ODN On Melanoma

Background Melanoma is a member of skin malignant tumors.It is urgent to find an effective treatment aiming at melanomas.Pimozide,a drug for acute and chronic schizophrenia,has been proved to have certain anti-melanoma effect as early as 1979,but its effect is limited.With the development of immunology,chemotherapy combined with immunotherapy for cancer has attracted more researchers' attention.As a TLR9 receptor agonist,CpG ODN has been proved to enhance the body's anti-tumor immune responses.Ipso facto,this study will investigate the anti-melanoma effects of CpG ODN combined with Pimozide.Objective Investigate the anti-melanoma effects of Pimozide combined with CpG ODN in mice and explore its underlying mechanism.Method Mouse melanoma model was established at a dose of 1 x 106/mouse.On the seventh day after the establishment of the model,mice were randomly divided into PBS group,Pimozide group,CpG ODN group and Pimozide combined CpG ODN group.CpG ODN was injected every other day and Pimozide was injected once a day for a week.Seven days after the last treatment,five mice were randomly executed in each group,and spleen and tumor tissues were collected.The size of tumors in mice was recorded.The expressions of MMP2,p-STAT5,CD4 and CD8 were detected by Western blot.The infiltration of CD4+T and CD8+T lymphocytes in tumors was detected by immunohistochemistry.The expressions of CD4+T,CD8+T and NK1.1 lymphocytes in spleen were detected by flow cytometry.After that,the mice model was established and treated again,and the survival time of mice was recorded.Result1.Pimozide combined with CpG ODN significantly increased the survival time and inhibited the growth of melanoma-bearing mice.2.Western blot results showed that Pimozide combined with CpG ODN decreased the expression of MMP2 and p-STAT5 in melanoma tissues.3.Western blot results showed that Pimozide combined with CpG ODN increased the expression of CD4 and CD8 in melanoma tissues.4.Immunohistochemical results showed that Pimozide combined with CpG ODN increased the infiltration of CD4+ and CD8+ T lymphocytes in melanoma tissues.5.Flow pattern showed that Pimozide combined with CpG ODN increased the recruitment of CD4+T,CD8+T and NK1.1 lymphocytes in spleens.Conclusion Pimozide combined with CpG ODN could effectively inhibit the growth of melanoma in mice,prolonged the survival period of melanoma-bearing mice,and increased the anti-tumor immune response of melanoma-bearing mice.This experiment provided a theoretical and experimental basis for a potential strategy over melanoma in clinic.