Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells

Fu, Ling; Guo, Liang; Zheng, Yanhua; Zhu, Zhenyu; Zhang, Mingyue; Zhao, Xiaohua; Cui, Hongxue

doi:10.3892/ol.2018.7933

Cited by 2 publications

(2 citation statements)

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“…To our knowledge, this is the first attempt to evaluate the effect of SOR on lung JNK and lung TNF-α and IL-1β levels in vivo after DEN administration. However, it has been reported that SOR reduces JNK expression in lung cancer cell lines in vitro [ 64 ], and it has therapeutic properties by reducing TNF-α and IL-1β levels in liver cancer [ 65 ]. It has also been reported that treatment of low concentrations of SOR significantly inhibits the proliferation of A549 tumor cells in vitro and suppressed tumor growth in vivo [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

et al. 2023

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According 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-α) and interleukin-1 beta (IL-1β) 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-α and IL-1β 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.

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Section: Discussionmentioning

confidence: 99%

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

et al. 2023

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“…There were no studies evaluating the effect of SOR on lung JNK and serum TNF-α and IL-1β levels after DEN administration in rats previously. However, it has been reported that sorafenib reduces JNK expression in lung cancer cell line in vitro [32], and it has therapeutic properties by reducing TNF-α and IL-1β levels in liver cancer [33]. It has also been reported that, treatment of low concentrations of SOR signi cantly inhibits the proliferation of A549 tumor cells in vitro and suppressed tumor growth in vivo [34].…”

Section: Discussionmentioning

confidence: 99%

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Lung Cancer

Çiçek

Hayme

Kuzucu

et al. 2022

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Background: This study was designed to assess the possible beneficial effects of sorafenib (SOR) in diethylnitrosamine (DEN) induced lung carcinogenesis in male rats and also to examine its probable mechanisms of action. Methods and results: A total of 30 adult male rats were divided into three groups as (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 samples were analyzed to determine SOX2 levels. Levels of TNF-α and IL-1β were measured in lung tissue supernatants. Lung sections were evaluated histopathologically. Also, COX-2 and JNK were analyzed by immunohistochemistry and immunofluorescence methods respectively. SOR reduced the level of SOX2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Furthermore, SOR reduced lung histopathological structure and suppressed COX-2 and JNK expressionConclusions: These results suggest that SOR reduces inflammation in the tumor microenvironment and decreases the level of SOX2 which has an important role in maintaining cancer stem cell properties.

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Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells

Cited by 2 publications

References 50 publications

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Lung Cancer

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