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The analgesic drug methadone is able to sensitize various tumors to chemotherapy. In this in vitro study, the influence of methadone to the effectiveness of ALA\u2010PDT for SCC (FADU) and glioblastoma (A172) was investigated on the protoporphyrin IX (PpIX) fluorescence, survival rates, apoptosis, and cell cycle phase, each with or without the presence of methadone. The production of PpIX was increased by methadone in FADU cells while it was decreased in A172 cells. The survival rates of both cell lines treated by ALA\u2010PDT were significantly reduced by the combination with methadone (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05). Methadone also significantly increased the percentage of apoptotic cells and improved the effect of ALA\u2010PDT on the cell cycle phase arrest in the G0\/G1 phase (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05). This study demonstrates the potential of methadone to influence the cytotoxic effect of ALA\u2010PDT for both SCC and glioblastoma cell lines.<\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio201800468-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.201800468","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T11:51:02Z","timestamp":1559130662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Methadone enhances the effectiveness of 5\u2010aminolevulinic acid\u2010based photodynamic therapy for squamous cell carcinoma and glioblastoma in vitro"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1854-0219","authenticated-orcid":false,"given":"Lei","family":"Shi","sequence":"first","affiliation":[{"name":"Laser\u2010Forschungslabor, LIFE Center, University 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