Abstract

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 tumorigenesis in 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 cells in 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 model in vivo, which might provide a novel therapeutic target and potential strategy for lung cancer treatment in the future.

中文翻译：

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抑制 CDC42 可减少巨噬细胞募集并抑制体内肺肿瘤发生

摘要

背景

细胞分裂控制 (CDC) 42 参与了多种癌症的调节。巨噬细胞募集在肿瘤的发病和发展中发挥着重要作用。然而，目前尚不清楚 CDC42 是否有助于体内巨噬细胞募集和肺肿瘤发生。

方法

小干扰 RNA (siRNA) 用于敲低 Lewis 肺癌 (LLC)1 中的 CDC42。评估了CDC42敲低LLC1细胞的侵袭能力。将具有CDC42靶向小发夹RNA（shRNA）的LLC1细胞接种到C57BL/6小鼠体内，建立荷瘤动物模型，测量肿瘤大小和转移相关蛋白。此外，模型中还确定了巨噬细胞在肿瘤部位的侵袭以及巨噬细胞趋化因子。

结果

当CDC42被敲低时，LLC1细胞的侵袭和转移能力显着降低。当体内接种 CDC42 敲低 LLC1 细胞时，肿瘤大小和转移相关蛋白水平均下降。巨噬细胞和相关的巨噬细胞趋化因子的侵袭能力也显着下调。

结论

我们的数据表明，抑制肺癌细胞中 CDC42 的表达可以显着阻止体内同种异体移植肿瘤模型中肿瘤的发病和发展，这可能为未来的肺癌治疗提供新的治疗靶点和潜在策略。