Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

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dc.authoridgul, mustafa/0000-0002-0042-890X
dc.authoridYeni, Yeşim/0000-0002-6719-7077
dc.authoridKuzucu, Mehmet/0000-0002-7786-7687
dc.authoridKantarci, Mecit/0000-0002-1043-6719
dc.authoridBolat, Ismail/0000-0003-1398-7046
dc.authoridTsatsakis, Aristidis/0000-0003-3824-2462
dc.authoridHayme, Serhat/0000-0001-9428-3002
dc.authorwosidgul, mustafa/G-5842-2011
dc.authorwosidGenç, Sıdıka/AHB-6098-2022
dc.authorwosidYeni, Yeşim/JTV-4518-2023
dc.authorwosidKuzucu, Mehmet/IZE-6900-2023
dc.authorwosidKantarci, Mecit/AAL-5940-2021
dc.authorwosidYildirim, Serkan/AAH-6721-2020
dc.authorwosidBolat, Ismail/AAU-9698-2021
dc.contributor.authorCicek, Betul
dc.contributor.authorHacimuftuoglu, Ahmet
dc.contributor.authorKuzucu, Mehmet
dc.contributor.authorCetin, Ahmet
dc.contributor.authorYeni, Yesim
dc.contributor.authorGenc, Sidika
dc.contributor.authorYildirim, Serkan
dc.date.accessioned2024-08-04T21:01:12Z
dc.date.available2024-08-04T21:01:12Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractAccording to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-alpha and IL-1 beta levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.en_US
dc.identifier.doi10.3390/ph16020221
dc.identifier.issn1424-8247
dc.identifier.issue2en_US
dc.identifier.pmid37259369en_US
dc.identifier.urihttps://doi.org/10.3390/ph16020221
dc.identifier.urihttps://hdl.handle.net/11616/104179
dc.identifier.volume16en_US
dc.identifier.wosWOS:000940924500001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofPharmaceuticalsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectlung carcinogenesisen_US
dc.subjectdiethylnitrosamineen_US
dc.subjectinflammationen_US
dc.subjectSOX-2en_US
dc.subjectCOX-2en_US
dc.subjectJNKen_US
dc.titleSorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuriesen_US
dc.typeArticleen_US

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