Effects of cardiopulmonary bypass on in vitro proliferation of human pancreatic cancer cells and plasma growth factor levels
摘要
Advances in medicine lead to an increase in the number of patients with concurrent heart disease and cancer. We investigated the effect of cardiac surgery under cardiopulmonary bypass (CPB) on the blood levels of growth factor cytokines, and assessed whether it might affect the proliferation of pancreatic cancer cells.
MethodsTen consenting patients undergoing elective cardiac surgery with the use of CPB under general anesthesia. We obtained patients’ serum at each of the following time points: between median sternotomy and before activating CPB (pre-CPB), and after activating CPB (post-CPB). Growth factor cytokines in plasma samples were analyzed using cytokine array. Proliferation assay was performed using pancreatic cancer cells (PANC-1 and PK-1) incubated in culture medium containing patients’ serum at a concentration of 30%. The levels of cytokines and proliferation of cancer cells were compared between pre-CPB and post-CPB samples.
ResultsPlasma and serum from eight patients were analyzed. PANC-1 and PK-1 cells proliferated significantly more following incubation with post-CPB (125%, P = 0.014 and 120%, P = 0.030, respectively) than pre-CPB samples. The following cytokines were significantly increased post-CPB compared to pre-CPB: amphiregulin (42 fold), basic fibroblast growth factor (5 fold), heparin binding-epidermal growth factor (9199 fold), hepatocyte growth factor (9 fold), insulin-like growth factor-binding protein (IGFBP)-1 (11 fold), IGFBP-4 (15 fold), insulin-like growth factor-2 (2 fold), macrophage colony-stimulating factor (2 fold), neurotrophin-4 (10 fold), transforming growth factor beta-3 (2 fold), vascular endothelial growth factor (VEGF)-A (3 fold), and VEGF receptor 2 (3 fold).
ConclusionsThese results suggest that cardiac surgery with CPB increases the plasma levels of several growth factors, thus potentially promoting pancreatic cancer cell proliferation, as seen in the in vitro study using serum from non-cancer patients.
Trial registrationregistration number UMIN000053046, date of registration December 12th, 2023.