Doxorubicin sensitizes breast cancer cells to natural killer cells in connection with increased Fas receptors
Issued Date
2022-03-01
Resource Type
ISSN
11073756
eISSN
1791244X
Scopus ID
2-s2.0-85124057926
Pubmed ID
35119077
Journal Title
International Journal of Molecular Medicine
Volume
49
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Medicine Vol.49 No.3 (2022)
Suggested Citation
Sawasdee N., Wattanapanitch M., Thongsin N., Phanthaphol N., Chiawpanit C., Thuwajit C., Yenchitsomanus P.T., Panya A. Doxorubicin sensitizes breast cancer cells to natural killer cells in connection with increased Fas receptors. International Journal of Molecular Medicine Vol.49 No.3 (2022). doi:10.3892/ijmm.2022.5095 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83808
Title
Doxorubicin sensitizes breast cancer cells to natural killer cells in connection with increased Fas receptors
Author's Affiliation
Other Contributor(s)
Abstract
Breast cancer (BC) is the most common cancer in women. Although standard treatments are successful in patients with BC diagnosed at an early stage, an alternative treatment is required for patients with advanced-stage disease who do not respond to these treatments. The concept of using chemotherapy to sensitize cancer cells to become susceptible to immunotherapy was recently introduced and may be used as an alternative treatment for BC. The chemotherapeutic drug doxorubicin has been reported to sensitize cancer cells; however, the efficacy to sensitize the solid spheroids, in addi- tion to its underlying mechanism regarding how doxorubicin sensitizes BC, has not previously been explored. In the present study, the effectiveness of a combined treatment of doxorubicin and natural killer-92 (NK-92) cells against BC in either 2d or 3d spheroid models, and its association with Fas receptor (FasR) expression, was demonstrated. The BC (MCF7) cell line expressing a higher level of FasR was more sensitive to NK-92 cell killing than the MDA-MB-231 cell line, which expressed a lower level of FasR. A sublethal dose of doxoru- bicin caused a significant improvement in NK cytotoxicity. concordantly, a significant reduction in cell viability was observed in the doxorubicin-treated McF7 spheroids. Notably, flow cytometric analysis revealed significantly increased FasR expression in the MCF7 cells, suggesting the underlying sensitization mechanism of doxorubicin in Bc was related to the FasR upregulation. The present findings supported the use of combined doxorubicin and NK immunotherapy in Bc treatment.