Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin

BMC Cancer

Bernhard Gillissen¹  Antje Richter¹  Frank Essmann²  Wolfgang Kemmner³ 

[1] Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin, Campus Berlin-Buch, Humboldt University, Berlin, Germany;Dr. Margarete-Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany, Auerbachstr. 112, 70376, Stuttgart, Germany;Research Group Translational Oncology, Experimental and Clinical Research Center at the Max- Delbrueck-Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany;

关键词: Photodynamic therapy;    Protoporphyrin-IX;    Ferrochelatase;    Alectinib;    Gastrointestinal carcinomas;   

DOI  :  10.1186/s12885-021-08667-x

来源: Springer

【 摘 要 】

BackgroundPhotodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX.MethodsTumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytometry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide to distinguish early apoptotic cells and late apoptotic/necrotic cells.ResultsHere, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death.ConclusionsThe usage of Alectinib could be another step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas.

【 授权许可】

CC BY