Effect of carbon dioxide pneumoperitoneum on human renal cell carcinoma proliferation and metastasis in an orthotropic xenograft nude mouse model

Introduction: This study aimed to explore the effect of carbon dioxide (CO2) pneumoperitoneum on tumor proliferation and metastasis in an orthotropic xenograft nude mice model of human renal cell carcinoma (RCC) and evaluate the safety of CO2 pneumoperitoneum laparoscopy for treating RCC. Material and methods: RCC 786-0 cells were injected to establish an orthotropic xenograft model. Fifty nude mice were given orthotropic inoculations and randomized to five groups: group A (control); group B (CO2 pneumoperitoneum for 2 h); group C (CO2 pneumoperitoneum for 4 h); group D (CO2 pneumoperitoneum for 4 h and 24 h after waking); group E (CO2 pneumoperitoneum for 4 h and 48 h after waking). The proliferation status was observed in RCC specimens by immunohistochemical staining for Ki67. The protein levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) were examined by western blotting. Results: All groups showed similar Ki67-positive staining in RCC samples (p > 0.05). The relative expression of HIF-1 alpha and VEGF gradually increased in both group B and group C, as compared with group A, but only the difference between group C and group A reached statistical significance (p < 0.05). The protein levels of HIF-1 alpha and VEGF decreased in both group D and group E, as compared with group B and group C; however, the differences between group D, group E, and group A did not reach statistical significance (p > 0.05). Conclusions: In an orthotropic xenograft nude mice model of RCC, CO2 pneumoperitoneum has no effect on expression of the cellular proliferation marker Ki67. However, CO2 pneumoperitoneum rapidly induces transient expression of HIF-1 alpha and VEGF. Thus, CO2 pneumoperitoneum laparoscopy may be a safe method for treating RCC.