Inhibition of CDC42 reduces macrophage recruitment and suppresses lung tumorigenesis in vivo

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.

Keywords:

• CDC42 knockdown
• macrophage invasion
• lung tumorigenesis
• allograft tumor
• Small interference RNA (siRNA)

Ethical approval

All the experiments were approved by the Ethics Committee of Zhejiang Hospital.

Author contributions

LLX and BZ conceived and designed the experiments, JZ, JL and LZ analyzed and interpreted the results of the experiments, YHX, XHZ and GPC performed the experiments.

Disclosure statement

The authors state that there are no conflicts of interest to disclose.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.