Inhibition Of Cdc42 Reduces Macrophage Recruitment And Suppresses Lung Tumorigenesis In Vivo

JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION(2021)

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摘要
Background Cell division control (CDC) 42 has been involved in the regulation of diverse cancers. Macrophage recruitment plays an important role in the pathogenesis and development of tumor. However, it remains unclear whether CDC42 contributes to macrophage recruitment and lung tumorigenesisin vivo. Methods Small interference RNA (siRNA) was used to knock down CDC42 in the Lewis lung carcinoma (LLC)1. The invasion capability of CDC42 knockdown LLC1 cells was evaluated. LLC1 cells with CDC42 targeted small hairpin RNA (shRNA) were inoculated into C57BL/6 mice to establish the tumor-bearing animal model Tumor size and metastasis related proteins were measured. In addition, the invasion of macrophages in the tumor site as well as macrophage chemokine were also determined in the model. Results The capacity of invasion and metastasis of LLC1 cells significantly decreased when CDC42 was knocked down. When inoculated with CDC42 knockdown LLC1 cellsin vivo, the tumor size and metastasis related proteins levels both decreased. The invasion capacity of macrophages and the associated macrophage chemokine were also significantly down-regulated. Conclusion Our data suggest that the inhibition of CDC42 expression in lung cancer cells can significantly prevent the pathogenesis and development of tumor in an allograft tumor modelin vivo, which might provide a novel therapeutic target and potential strategy for lung cancer treatment in the future.
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关键词
CDC42 knockdown, macrophage invasion, lung tumorigenesis, allograft tumor, Small interference RNA (siRNA)
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