| Autor: |
Wei, Cang, Anyue, Wu, Liying, Gu, Wenjing, Wang, Qi, Tian, Zhong, Zheng, Lihua, Qiu |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
International Immunopharmacology. 113:109422 |
| ISSN: |
1567-5769 |
| DOI: |
10.1016/j.intimp.2022.109422 |
| Popis: |
Erastin is a small molecule identified in chemical screen that is capable of inducing ferropotosis. There is collective evidence proving that erastin-induced ferroptosis exhibits anti-tumor potential within diverse caners, such as ovarian cancer (OC). However, most OC cells show relative resistance to ferroptosis induced by erastin. M2-polarized tumor-associated macrophages (TAMs) have an important effect on the OC tumor microenvironment (TME), which makes M2 polarization a noticeable part in the context of OC therapy. The immunomodulatory effects of erastin on ferroptosis-resistant OC cells remain poorly understood. Here, we found that low concentration of erastin greatly promoted ferroptosis-resistant OC cell invasion and migration via STAT3-mediated M2 polarization of macrophages. As revealed by in-vitro experimental results, erastin significantly increased metastases of ferroptosis-resistant OC, and the percentage of M2 macrophage infiltration was also raised after erastin treatment. Furthermore, erastin augmented IL-8 production of macrophages, and pharmacological blockage of IL-8 partially abrogated the stimulatory effect of erastin on ferroptosis-resistant OC cells. This study demonstrates a new mechanism undering the tumor-promoting activity of erastin and has implications for the STAT3/IL-8 axis as a potential target for ferroptosis-resistant OC cells to improve overall anti-tumor efficacy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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