Decreased Lung Tumor Development in SwAPP Mice through the Downregulation of CHI3L1 and STAT 3 Activity via the Upregulation of miRNA342-3p

Peroxiredoxin 4 (PRDX4), initially reported as an antioxidant, is overexpressed in lung cancer and participates in its progression. However, its role in the urethane-induced lung tumor model is undetermined. The aim of this study was to investigate the effect of PRDX4 overexpression on carcinogen-induced lung tumor development. Human PRDX4 overexpression transgenic (Tg) mice (hPRDX4+/+) and non-Tg mice were intraperitoneally injected with urethane to induce lung tumor. After 6 months, tumor formation was compared between groups and possible mechanisms for the difference in tumor development were investigated. The serum and lung PRDX4 expressions were enhanced after urethane stimulation in Tg mice. Both the average number of tumors (≥0.5 mm) and tumor diameter per mouse in the Tg group were significantly larger than in non-Tg controls, while body weight was lower in the Tg group. Compared with non-Tg controls, tumor cell proliferation was enhanced, while tumor cell apoptosis was suppressed in Tg mice. Systemic oxidative stress and oxidative stress in lung tumors were inhibited by PRDX4 overexpression. The balance of prooxidant enzymes and antioxidant enzymes was also shifted to a decreased level in Tg tumor. In lung tumor tissue, the density of microvessel penetrated into tumor was higher in the Tg group; macrophage infiltration was enhanced in Tg tumors, while there was no difference in T lymphocyte infiltration; the expressions of cytokines, including interleukin-1 beta (IL-1β) and matrix metallopeptidase 9 (MMP9), were elevated in Tg tumors, which resulted from enhanced phosphorylation of nuclear factor-κB p65 (NF-κB p65) and c-Jun, respectively. In conclusion, PRDX4 overexpression modulated tumor microenvironment and promoted tumor development in the mouse urethane-induced lung cancer model.

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Dexmedetomidine Associated Lung Cancer Proliferation and Tumor Growth is Prevented by β-Caryophyllene: Role of AMPK Activation and PGC-1α/TFAM Over Expression

Indian Journal of Animal Research ◽

10.18805/ijar.bf-1431 ◽

2022 ◽

Author(s):

Dan Wang ◽

Dazhi Long ◽

Jiegang Zhou ◽

Ziqiang Dong ◽

Guiming Huang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Lung Tumor ◽

Apoptotic Cell ◽

Tumor Development ◽

A549 Cells ◽

Treated Group ◽

Metastatic Progression ◽

Cancer Proliferation

Background: Dexmedetomidine has been reported to induce anti-apoptotic effects and metastatic progression in lung cancer. In the current investigation, the effect of β-Caryophyllene on dexmedetomidine induced cell proliferation and apoptosis of lung cancer cells and tumor growth in mice was studied. Methods: A549 cell line was cultured with either dexmedetomidine alone or together with β-Caryophyllene for 24 h and analysed for cell proliferation with MTT assay. ELISA based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of target proteins. The induction of experimental lung tumor in rat model was achieved through the injection of A549 tumor cells subcutaneously into the middle left side of the mice after anesthetization with pentobarbital (35 mg/kg) at 2.8 × 106 cells in 400 μl of PBS. Result: We found that β-Caryophyllene exerts the anti-proliferative effects on A549 cells. Furthermore, β-Caryophyllene significantly prevents apoptotic cell death and causes up-regulation of PGC-1α and TFAM compared to dexmedetomidine treated cells. We observed that β-Caryophyllene suppressed tumor development in mice significantly compared to dexmedetomidine treated group without changing body weight.

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The ERBB network facilitates KRAS-driven lung tumorigenesis

10.1101/290700 ◽

2018 ◽

Cited By ~ 1

Author(s):

Björn Kruspig ◽

Tiziana Monteverde ◽

Sarah Neidler ◽

Andreas Hock ◽

Emma Kerr ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tumor ◽

Tumor Development ◽

Treatment Strategies ◽

Invasive Disease ◽

Therapeutic Benefit ◽

Lung Tumors ◽

Network Activity ◽

Lung Tumorigenesis

AbstractKRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling, however recent data suggest that this independence may not be absolute. Here we show that initiation and progression of KRAS-driven lung tumors requires input from ERBB family RTKs: Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRasG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS mutant tumor cells in culture and progression to invasive disease in vivo. Importantly, brief pharmacological inhibition of the ERBB network significantly enhances the therapeutic benefit of MEK inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.One Sentence SummaryG12 Mutant KRAS requires tonic ERBB network activity for initiation and maintenance of lung cancer

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