Study On The Effect And Mechanism Of Cheng-Qi-Jie-Yi-Tang On Pancreatic Cancer

Objective:Inflammation plays an important role in the progression of pancreatic cancer.Our previous study found that Cheng-Qi-Jie-Yi-Tang(CQJYT)has anti-inflammatory effect.In clinical application,combined with chemotherapy can reduce the clinical symptoms of pancreatic cancer patients,and enhance the efficiency of chemotherapeutic drugs.In this study,we mainly study the therapeutic effect of CQJYT on pancreatic cancer,and explore whether the decoction can improve the tumor microenvironment(TME)by inhibiting inflammation and thus play a role in inhibiting pancreatic cancer.Method:1.The orthotopic xenograft tumor model of pancreatic cancer was established by the pancreatic cancer PANC-1 cell line suspension in nude mice.2.Luminex technology was used to detect the average fluorescence intensity of mouse transplanted tumors.3.Immunohistochemistry was used to detect the expression of CD68,CD163 and Ki-67 in pancreatic cancer xenografts.4.The proportion of CD68+/CD163+/CD206+ cell populations in macrophages was detected by flow cytometry.5.Use microarray and bioinformatics methods for GO analysis and pathway analysis.6.Real-time PCR was used to detect the expression of CD24,CD44 and EPCAM in pancreatic cancer cells.7.Flow cytometry was used to detect the expression of CD24,CD44 and EPCAM and the proportion of CD44+/CD24+/EPCAM+ cell populations in pancreatic cancer cells.8.The mouse model of chronic pancreatitis was established by tail vein injection of dibutyltin dichloride(DBTC).9.SPSS 22.0 software was used to analyze the experimental data,and chi-square test and group t test were used to analyze the intra-group and inter-group differences.Result:1.CQJYT can inhibit the growth of pancreatic cancer tumor in tumor-bearing mice.2.CQJYT reduced the expression of Ki-67 in transplanted tumors of nude mice.3.CQJYT reduced the infiltration of CD68 and CD163 positive cells in nude mice transplanted tumor tissue.4.CQJYT reduced the proportion of M2 macrophages in vitro.5.CQJYT affects the expression of multiple differentiation-related genes in macrophages,and mainly inhibits macrophage differentiation through PI3K-AKT,m TOR and other signaling pathways.6.Macrophage conditioned medium(MCM)promoted the expression of stemness in PANC-1cells.7.The macrophage conditional medium(MCM)increased the proportion of CD44+/CD24+/EPCAM+ cell populations in pancreatic cancer cells.8.The anti-tumor effect is played by the inflammatory microenvironment.The nude mice with inflammatory foundation can play a synergistic role with the combination of the decoction and the gemcitabine.However,there was no synergistic effect in the tumor models without inflammation.Conclusion:CQJYT inhibits macrophage differentiation through PI3K-AKT,m TOR and other signaling pathways,reduces the infiltration of M2 tumor-associated macrophages(TAMs),and then plays a role in inhibiting the development of pancreatic cancer.In addition,this experiment confirmed that MCM can upregulate the stemness of pancreatic cancer stem cells.It is presumed that the decoction may also indirectly involves in down-regulating the stemness of pancreatic cancer stem cells(CSCs)by reducing TAMs,and increase the sensitivity to chemotherapy.This provides a new idea for the treatment of pancreatic cancer.