Article ; Online: Low-dose aspirin can inhibit exosomal release induced by radiotherapy in breast cancer and attenuate its inhibitory effect on NK cell proliferation.
2023 Volume 12, Issue 15, Page(s) 16386–16404
Abstract: Background: Breast cancer (BC) seriously threatens women's health. Aspirin plays a key role in the treatment and prognosis of BC.: Objective: To explore the effect of low-dose aspirin on BC radiotherapy through the mechanism of exosomes and natural ... ...
| Abstract | Background: Breast cancer (BC) seriously threatens women's health. Aspirin plays a key role in the treatment and prognosis of BC. Objective: To explore the effect of low-dose aspirin on BC radiotherapy through the mechanism of exosomes and natural killer (NK) cells. Methods: BC cells were injected into the left chest wall to establish a BC model in nude mice. Tumor morphology and size were observed. Immunohistochemical staining for Ki-67 was used to observe the proliferation of tumor cells. TUNEL was used to detect the apoptosis of cancer cells. Protein levels of exosomal biogenesis- and secretion-related genes (Rab 11, Rab27a, Rab27b, CD63, and Alix) were detected by Western blot. Flow cytometry was used to detect apoptosis. Transwell assays were used to detect cell migration. A clonogenic assay was used to detect cell proliferation. Exosomes of BT549 and 4T1-Luc cells were extracted and observed by electron microscopy. After the coculture of exosomes and NK cells, the activity of NK cells was detected by CCK-8. Results: The protein expression of genes related to exosomal genesis and secretion (Rab 11, Rab27a, Rab27b, CD63, and Alix) in BT549 and 4T1-Luc cells was upregulated under radiotherapy treatment. Low doses of aspirin inhibited exosome release from BT549 and 4T1-Luc cells and alleviated the inhibitory effect of BC cell exosomes on NK cell proliferation. In addition, knocking down Rab27a reduced the protein levels of exosome-related and secretion-related genes in BC cells, further enhancing the promotive effect of aspirin on NK cell proliferation, while overexpressing Rab27a had the opposite effect. Aspirin was combined at a radiotherapeutic dose of 10 Gy to enhance the radiotherapy sensitivity of radiotherapy-tolerant BC cells (BT549R and 4T1-LucR). Animal experiments have also verified that aspirin can promote the killing effect of radiotherapy on cancer cells and significantly inhibit tumor growth. Conclusion: Low doses of aspirin can inhibit the release of BC exosomes induced by radiotherapy and weaken their inhibition of NK cell proliferation, promoting radiotherapy resistance. |
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| MeSH term(s) | Animals ; Mice ; Female ; Mice, Nude ; Aspirin/pharmacology ; Cell Proliferation ; Cell Movement ; Exosomes/metabolism ; Cell Line, Tumor ; Neoplasms/metabolism |
| Chemical Substances | Aspirin (R16CO5Y76E) |
| Language | English |
| Publishing date | 2023-07-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2659751-2 |
| ISSN | 2045-7634 ; 2045-7634 |
| ISSN (online) | 2045-7634 |
| ISSN | 2045-7634 |
| DOI | 10.1002/cam4.6274 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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