Effect Of General Anesthetics On Lung Metastasis Of Circulating-Tumor Cell For Colorectal Cancer In Mice

Background:At present,the number of patients with colorectal cancer in China is increasing rapidly.Its mortality rate is only second to gastric cancer,esophageal cancer and liver cancer in malignant tumors of digestive system,which seriously threatens the life and health of patients.Sxirgery is often used as the main treatment for the early stage of CRC.The most common metastatic organ of colorectal cancer is liver,followed by lung.Once metastasis occurs,it often indicates that the long-term prognosis of patients is not satisfactory.Anesthesia,as an important part of perioperative period,will also have a certain impact on the prognosis of cancer patients undergoing surgery.Many studies have shown that general anesthetics widely used in clinic can affect the metastasis and recurrence of tumors.During the resection of CRC,even if the primary tumor is completely removed,there may still have CTCs in circulation,which may cause metastasis of patients.Therefore,we explore the effect of propofol and sevoflxirane on pulmonary metastasis of CTCs for CRC after surgery.Method:1.Ii order to simulate the process of circulating tumor cells releasing for patients who receiving colorectal cancer resection under propofol or sevoflurane,CT-26 cells were injected into the tail vein of BALB/c mice.40 mice were divided into 4 groups;these mice were given intraperitoneal injection of propofol(20ul/g),inhalation of sevoflurane(1.8-2%,2hrs),intraperitoneal injection of saline(20ul/g),intraperitoneal injection of lipid emulsion(20ul/g),respectively.The number of metastatic foci on the lung surface was counted after 14 days to investigate the effects of propofol and sevoflurane on lung metastasis of colorectal circulating tumor cells in mice.2.In vitro,different concentrations of propofol and 20%lipid emulsion was used to treat two groups of CT-26 cells(2*105,5*105).Then the proportion of living cells in two groups was counted with cell counter after 2 hours.3.In vivo,CT-26 cells collected from vitro experiment were injected into the tail veins of BALB/c mice after 14 days.Then we counted the number of metastatic foci on the lung surface to determine the effect of propofol on circulating tumor cells for colorectal cancer.Ki-67 and TUNEL was used to examine the proliferation and apoptosis for exploring the effect of propofol exerting on circulating tumor cells.Result:The average number of metastatic foci on the lung surface in each group was 4 in saline group,16.5 in propofol group,3.7 in sevoflurane group and 8 in fat emulsion group.Compared with mice incubated with 20%lipid emulsion(25ul/ml)and 0.9%saline(50 ul/ml),lung metastases of mice incubated with propofol(5ul/ml)were significantly increased(P<0.001).This phenomenon can also be found in propofol(10 ul/ml,n=5),but it is relatively weak(P<0.05).In the Ki-67,the expression rate of Ki-67 in propofol(5ul/ml,n=5)group was significantly higher than that in blank group(P<0.01).The propofol group(10 ul/ml,n=5)had similar phenomena,but was relatively weak(P<0.05).There was no significant difference between fat emulsion group and blank group.There was no statistical difference for the results of TUNEL,either.Conclusion:We found that,in BALB/c mice,propofol could promote the lung metastasis of circulating tumor cells for CT-26 cells while sevoflurane does not have this effect.Circulating tumor cells for CT-26 cells achieved this process by promoting its proliferation rather than inhibiting its apoptosis.