Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells
Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells
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DOI：
10.1002/mnfr.201200610
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发表时间：
2013-06-01
影响因子：
5.2
通讯作者：
Komohara, Yoshihiro
中科院分区：
文献类型：
--
作者：
Horlad, Hasita;Fujiwara, Yukio;Komohara, Yoshihiro
最近的研究表明，骨髓细胞与肿瘤宿主的全身免疫抑制有关。特别是，荷瘤小鼠中Gr-1和CD 11b阳性的骨髓细胞被称为髓源性抑制细胞（MDSC），因为它们抑制T细胞活化。本研究采用小鼠肉瘤模型研究科罗索酸（CA）的抗肿瘤作用。方法和结果体内研究的结果表明，CA给药并不抑制肿瘤增殖指数，但显着削弱皮下肿瘤的发展和肺转移。此外，CA管理抑制信号转导和转录激活因子-3（Stat 3）的激活，并增加肿瘤组织中浸润淋巴细胞的数量。体外分析表明，一个显着的MDSC荷瘤小鼠的免疫抑制作用被废除，并在MDSC中的环氧合酶-2和CCL 2的mRNA表达显着降低CA管理。此外，CA在体外增强阿霉素和顺铂的抗肿瘤作用。结论Stat 3不仅在骨肉瘤中与肿瘤进展相关，而且在其他恶性肿瘤中也与肿瘤进展相关，提示CA可能通过靶向MDSC的免疫抑制活性及其与抗癌药物的协同作用而广泛用于抗肿瘤治疗。
Scope Recent studies demonstrated that myeloid cells are associated with systemic immunosuppression in tumor-bearing hosts. In particular, myeloid cells positive for Gr-1 and CD11b in tumor-bearing mice are called myeloid-derived suppressor cells (MDSC) because of their suppression of T-cell activation. In this study, we investigated the antitumor effects of corosolic acid (CA) in murine sarcoma model. Methods and results The results from the in vivo study showed that CA administration did not suppress the tumor proliferation index, but significantly impaired subcutaneous tumor development and lung metastasis. Furthermore, CA administration inhibited signal transducer and activator of transcription-3 (Stat3) activation and increased in the number of infiltrating lymphocytes in tumor tissues. Ex vivo analysis demonstrated that a significant immunosuppressive effect of MDSC in tumor-bearing mice was abrogated and the mRNA expressions of cyclooxygenase-2 and CCL2 in MDSC were significantly decreased by CA administration. Furthermore, CA enhanced the antitumor effects of adriamycin and cisplatin in in vitro. Conclusion Since Stat3 is associated with tumor progression not only in osteosarcoma, but also in other malignant tumors, our findings indicate that CA might be widely useful in anticancer therapy by targeting the immunosuppressive activity of MDSC and through its synergistic effects with anticancer agents.