Inhibitory Effect of Dihydroartemisinin on the Proliferation and Migration of Melanoma Cells and Experimental Lung Metastasis From Melanoma in Mice.
Inhibitory Effect of Dihydroartemisinin on the Proliferation and Migration of Melanoma Cells and Experimental Lung Metastasis From Melanoma in Mice.
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DOI：
10.3389/fphar.2021.727275
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发表时间：
2021
影响因子：
5.6
通讯作者：
Jin G
中科院分区：
文献类型：
--
作者：
Zhang Q;Jin L;Jin Q;Wei Q;Sun M;Yue Q;Liu H;Li F;Li H;Ren X;Jin G
黑色素瘤是侵袭性的，并且可以在肿瘤的早期阶段转移。双氢青蒿素（DHA）对肿瘤的治疗有积极作用，且无明显毒副作用。我们以前的研究表明，DHA可以抑制黑色素瘤的形成。然而，DHA如何影响黑色素瘤的侵袭和转移仍然不清楚。在本研究中，将使用B16 F10和A375细胞系和转移性肿瘤模型来研究DHA的作用。本研究结果表明，DHA抑制A375和B16 F10细胞的增殖能力。正如预期的那样，DHA给药后A375和B16 F10细胞的迁移能力也降低。DHA可减轻小鼠黑色素瘤的严重程度和组织病理学变化。DHA诱导肿瘤微环境中CD8+CTL的扩增。相反，DHA抑制Treg细胞浸润到肿瘤微环境中。DHA通过调节FasL表达和颗粒酶B分泌促进黑色素瘤细胞凋亡。此外，DHA影响肿瘤组织中STAT3诱导的EMT和MMPS。此外，代谢组学分析表明，DHA给药后PGD2和EPA显著增加。因此，DHA在体内外均能抑制黑色素瘤的增殖、迁移和转移。这些结果对DHA在治疗人类黑色素瘤中的潜在用途具有重要意义。
Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8+CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8+CTLs. Moreover, DHA impacts STAT3-induced EMT and MMPS in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma in vitro and in vivo. These results have important implications for the potential use of DHA in the treatment of melanoma in humans.
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