A self-designed CpG ODN enhanced the anti-melanoma effect of pimozide

被引:7
|
作者
Jia, Huijie [1 ,2 ,3 ]
Guo, Jing [1 ]
Wang, Pingping [4 ]
Sun, Ke [3 ]
Chen, Jian [4 ]
Ren, Wenjing [5 ]
Wei, Tian [4 ]
Yang, Yunfan [1 ]
Li, Jie [1 ]
Liu, Xiaoming [1 ]
Li, Ruipeng [1 ]
Zhong, Jiateng [1 ,2 ,3 ]
Wang, Mingyong [6 ]
Tian, Zhongwei [5 ]
Feng, Zhiwei [1 ,2 ,4 ]
Zhao, Tiesuo [1 ,2 ,4 ]
机构
[1] Xinxiang Med Univ, Inst Precis Med, 601 Jinsui Rd, Xinxiang 453007, Henan, Peoples R China
[2] Xinxiang Med Univ, Xinxiang Key Lab Tumor Vaccine & Immunotherapy, Xinxiang, Henan, Peoples R China
[3] Xinxiang Med Univ, Dept Pathol, Xinxiang, Henan, Peoples R China
[4] Xinxiang Med Univ, Dept Immunol, Xinxiang, Henan, Peoples R China
[5] Xinxiang Med Univ, Dept Dermatol, Affiliated Hosp 1, Xinxiang, Henan, Peoples R China
[6] Xinxiang Med Univ, Dept Lab Med, Xinxiang, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
CpG ODN; Melanoma; Pimozide; Immunotherapy; STAT; ANTITUMOR IMMUNE-RESPONSE; PHASE-II TRIAL; INTRATUMORAL INJECTION; MALIGNANT-MELANOMA; STAT5; CONTRIBUTES; GENE-EXPRESSION; ACTIVATION; OLIGODEOXYNUCLEOTIDE; IMMUNOTHERAPY; DELIVERY;
D O I
10.1016/j.intimp.2020.106397
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Melanomas represent the deadliest form of skin cancers. Due to the intricacy of tumorigenesis, it is emergent to find effective therapies for melanomas. Researches have proved that pimozide inhibits the growth of melanoma, but the limited curing effect needs to be further improved. Nowadays, tumor immunotherapy has been widely recognized as the sole therapy that can eradicate cancers. Cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN), TLR9 receptor agonist, can significantly enhance anti-tumor immune responses. This study explored the therapeutic effect of pimozide combined with CpG ODN on melanoma-bearing mice. The results showed that pimozide combined with CpG ODN effectively inhibited the growth of melanoma and prolonged the survival of melanoma-bearing mice, inhibited the expression of MMP2 and p-Stat5, increased the infiltration of CD4(+) and CD8(+) T cells in tumor, raised the ratios of CD4(+), CD8(+) T cells and NK cells. These all indicated that the combination treatment improved the anti-tumor effect of pimozide on mice. The anti-tumor mechanism might be attributed to cell apoptosis induction, invasion inhibition, and immune regulation. A more effective combination treatment concerning with pimozide is being under investigation.
引用
收藏
页数:9
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