Abstract
Background: Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancerrelated deaths in women. Activation of EGFR by EC-secreted EGFR ligands promotes breast cancer progression. Current treatments provide limited benefits in triple-negative breast cancer (TNBC). Photodynamic therapy (PDT) has been proven effective for the treatment of TNBC through the EGFR pathway, but the underlying mechanism is still unclear.
Purpose: The purpose of this study was to determine the role of the EGFR pathway in the treatment of PDT on TNBC in a co-culture system.
Methods: MB-231 and HUVEC were co-cultured for experiments (HU-231). Cell viability and ROS production were detected after AE-PDT, a combination of EGFR inhibitors (AEE788)with PDT to test angiogenesis, apoptosis, and pyroptosis. WB detects expression of EGFR. EGFR, P-EGFR, VEGF, caspase-1, capase-3, and GSDMD .
Results: AE-PDT inhibited HU-231 cell proliferation and tumor angiogenesis, and induced cell apoptosis and pyroptosis by promoting ROS production. AEE788, an inhibitor of the EGFR, enhanced HU-231 cell killing after AE-PDT.
Conclusion: Our study suggested that the combination of EGFR inhibitors and AE-PDT could synergistically suppress breast cancer progression, providing a new treatment strategy.
Graphical Abstract
[http://dx.doi.org/10.1177/0897190012442062] [PMID: 22551559]
[http://dx.doi.org/10.3389/fonc.2021.643394] [PMID: 33996559]
[http://dx.doi.org/10.1016/1040-8428(94)00144-I] [PMID: 7612182]
[PMID: 9816062]
[http://dx.doi.org/10.1046/j.1523-1755.2002.00631.x] [PMID: 12371954]
[http://dx.doi.org/10.1038/nrc2088] [PMID: 17318210]
[http://dx.doi.org/10.3389/fonc.2012.00031] [PMID: 22645717]
[http://dx.doi.org/10.1016/j.pdpdt.2015.04.004] [PMID: 25930668]
[http://dx.doi.org/10.3390/cancers12102732] [PMID: 32977602]
[http://dx.doi.org/10.1016/j.ajps.2022.01.003] [PMID: 35582644]
[http://dx.doi.org/10.3390/molecules25235666] [PMID: 33271809]
[http://dx.doi.org/10.1007/978-1-4419-8871-3_1] [PMID: 15015550]
[PMID: 18695894]
[http://dx.doi.org/10.18632/oncotarget.7961] [PMID: 26967052]
[http://dx.doi.org/10.2165/00003495-200060001-00002] [PMID: 11129168]
[http://dx.doi.org/10.1038/s41416-019-0573-8] [PMID: 31564718]
[http://dx.doi.org/10.1021/acsami.8b04163] [PMID: 29737828]
[http://dx.doi.org/10.1016/j.jphotobiol.2009.04.001] [PMID: 19406659]
[http://dx.doi.org/10.1038/sj.onc.1204313] [PMID: 11402326]
[http://dx.doi.org/10.1002/jcb.22366] [PMID: 19816982]
[http://dx.doi.org/10.4161/cbt.8.14.8693] [PMID: 19421004]
[http://dx.doi.org/10.4161/cbt.22256] [PMID: 22986230]
[http://dx.doi.org/10.1023/A:1006367032156] [PMID: 10638483]
[http://dx.doi.org/10.1002/(SICI)1096-9896(199908)188:4<369:AID-PATH381>3.0.CO;2-X] [PMID: 10440746]