Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

A Combination of EGFR Inhibitors and AE-PDT Could Synergistically Suppress Breast Cancer Progression

Author(s): Yajuan Niu, Xiya Guo, Wang Han, Xiaoyu Han, Kaiting Li, Si Tian, Ying Zhu, DingQun Bai and Qing Chen*

Volume 23, Issue 19, 2023

Published on: 14 September, 2023

Page: [2135 - 2145] Pages: 11

DOI: 10.2174/1871520623666230908145748

open access plus

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.

Keywords: EGFR pathway, photodynamic therapy (PDT), apoptosis, pyroptosis, angiogenesis, breast cancer.

Graphical Abstract
[1]
Griffiths, C.L.; Olin, J.L. Triple negative breast cancer: A brief review of its characteristics and treatment options. J. Pharm. Pract., 2012, 25(3), 319-323.
[http://dx.doi.org/10.1177/0897190012442062] [PMID: 22551559]
[2]
Zhang, Y.; Sun, Y.; Ding, L.; Shi, W.; Ding, K.; Zhu, Y. Long non-coding RNA LINC00467 correlates to poor prognosis and aggressiveness of breast cancer. Front. Oncol., 2021, 11, 643394.
[http://dx.doi.org/10.3389/fonc.2021.643394] [PMID: 33996559]
[3]
Salomon, D.S.; Brandt, R.; Ciardiello, F.; Normanno, N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol., 1995, 19(3), 183-232.
[http://dx.doi.org/10.1016/1040-8428(94)00144-I] [PMID: 7612182]
[4]
Uhlman, D.L.; Nguyen, P.; Manivel, J.C.; Zhang, G.; Hagen, K.; Fraley, E.; Aeppli, D.; Niehans, G.A. Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: Correlation with metastatic behavior and prognosis. Clin. Cancer Res., 1995, 1(8), 913-920.
[PMID: 9816062]
[5]
Sutton, T.A.; Fisher, C.J.; Molitoris, B.A. Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int., 2002, 62(5), 1539-1549.
[http://dx.doi.org/10.1046/j.1523-1755.2002.00631.x] [PMID: 12371954]
[6]
Sharma, S.V.; Bell, D.W.; Settleman, J.; Haber, D.A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer, 2007, 7(3), 169-181.
[http://dx.doi.org/10.1038/nrc2088] [PMID: 17318210]
[7]
Mehta, V.K. Radiotherapy and erlotinib combined: review of the preclinical and clinical evidence. Front. Oncol., 2012, 2, 31.
[http://dx.doi.org/10.3389/fonc.2012.00031] [PMID: 22645717]
[8]
Kawczyk-Krupka, A.; Bugaj, A.M.; Latos, W.; Zaremba, K.; Wawrzyniec, K.; Sieroń, A. Photodynamic therapy in colorectal cancer treatment: The state of the art in clinical trials. Photodiagn. Photodyn. Ther., 2015, 12(3), 545-553.
[http://dx.doi.org/10.1016/j.pdpdt.2015.04.004] [PMID: 25930668]
[9]
Mashayekhi, V.; Xenaki, K.T. van Bergen en Henegouwen, P.M.P.; Oliveira, S. Dual targeting of endothelial and cancer cells potentiates in vitro nanobody-targeted photodynamic therapy. Cancers, 2020, 12(10), 2732.
[http://dx.doi.org/10.3390/cancers12102732] [PMID: 32977602]
[10]
Chen, C.; Yang, S.; Liu, Y.; Qiu, Y. Yao, J. Metal ions-bridged Jaggregation mediated nanoassembly composition for breast cancer phototherapy. Asian J. Pharma. Sci., 2022, 17(2), 230-240.
[http://dx.doi.org/10.1016/j.ajps.2022.01.003] [PMID: 35582644]
[11]
Verebová, V.; Beneš, J.; Staničová, J. Biophysical characterization and anticancer activities of photosensitive phytoanthraquinones represented by hypericin and its model compounds. Molecules, 2020, 25(23), 5666.
[http://dx.doi.org/10.3390/molecules25235666] [PMID: 33271809]
[12]
Patan, S. Vasculogenesis and angiogenesis. Cancer Treat. Res., 2004, 117, 3-32.
[http://dx.doi.org/10.1007/978-1-4419-8871-3_1] [PMID: 15015550]
[13]
Mukherjee, B.; Mayer, D. Dihydrotestosterone interacts with EGFR/MAPK signalling and modulates EGFR levels in androgen receptor-positive LNCaP prostate cancer cells. Int. J. Oncol., 2008, 33(3), 623-629.
[PMID: 18695894]
[14]
Li, X.; Wu, C.; Chen, N.; Gu, H.; Yen, A.; Cao, L.; Wang, E.; Wang, L. PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma. Oncotarget, 2016, 7(22), 33440-33450.
[http://dx.doi.org/10.18632/oncotarget.7961] [PMID: 26967052]
[15]
Raymond, E.; Faivre, S.; Armand, J.P. Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs, 2000, 60(1), 15-23.
[http://dx.doi.org/10.2165/00003495-200060001-00002] [PMID: 11129168]
[16]
Leonetti, A.; Sharma, S.; Minari, R.; Perego, P.; Giovannetti, E.; Tiseo, M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br. J. Cancer, 2019, 121(9), 725-737.
[http://dx.doi.org/10.1038/s41416-019-0573-8] [PMID: 31564718]
[17]
Wei, X.; Liu, L.; Guo, X.; Wang, Y.; Zhao, J.; Zhou, S. Light-activated ros-responsive nanoplatform codelivering apatinib and doxorubicin for enhanced chemo-photodynamic therapy of multidrug-resistant tumors. ACS Appl. Mater. Interfaces, 2018, 10(21), 17672-17684.
[http://dx.doi.org/10.1021/acsami.8b04163] [PMID: 29737828]
[18]
Robertson, C.A.; Evans, D.H.; Abrahamse, H. Photodynamic therapy (PDT): A short review on cellular mechanisms and cancer research applications for PDT. J. Photochem. Photobiol. B, 2009, 96(1), 1-8.
[http://dx.doi.org/10.1016/j.jphotobiol.2009.04.001] [PMID: 19406659]
[19]
Ahmad, N.; Kalka, K.; Mukhtar, H. In vitro and in vivo inhibition of epidermal growth factor receptor-tyrosine kinase pathway by photodynamic therapy. Oncogene, 2001, 20(18), 2314-2317.
[http://dx.doi.org/10.1038/sj.onc.1204313] [PMID: 11402326]
[20]
Koon, H.K.; Chan, P.S.; Wong, R.N.S.; Wu, Z.G.; Lung, M.L.; Chang, C.K.; Mak, N.K. Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cells. J. Cell. Biochem., 2009, 108(6), 1356-1363.
[http://dx.doi.org/10.1002/jcb.22366] [PMID: 19816982]
[21]
Chung, P.S.; He, P.; Shin, J.I.; Hwang, H.J.; Lee, S.J.; Ahn, J.C. Photodynamic therapy with 9-hydroxypheophorbide α on AMC-HN-3 human head and neck cancer cells: Induction of apoptosis via photoactivation of mitochondria and endoplasmic reticulum. Cancer Biol. Ther., 2009, 8(14), 1343-1351.
[http://dx.doi.org/10.4161/cbt.8.14.8693] [PMID: 19421004]
[22]
Edmonds, C.; Hagan, S.; Gallagher-Colombo, S.M.; Busch, T.M.; Cengel, K.A. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3. Cancer Biol. Ther., 2012, 13(14), 1463-1470.
[http://dx.doi.org/10.4161/cbt.22256] [PMID: 22986230]
[23]
Dimitroff, C.J.; Klohs, W.; Sharma, A.; Pera, P.; Driscoll, D.; Veith, J.; Steinkampf, R.; Schroeder, M.; Klutchko, S.; Sumlin, A.; Henderson, B.; Dougherty, T.J.; Bernacki, R.J. Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy. Invest. New Drugs, 1999, 17(2), 121-135.
[http://dx.doi.org/10.1023/A:1006367032156] [PMID: 10638483]
[24]
Decaussin, M.; Sartelet, H.; Robert, C.; Moro, D.; Claraz, C.; Brambilla, C.; Brambilla, E. Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): Correlation with angiogenesis and survival. J. Pathol., 1999, 188(4), 369-377.
[http://dx.doi.org/10.1002/(SICI)1096-9896(199908)188:4<369:AID-PATH381>3.0.CO;2-X] [PMID: 10440746]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy