Paeoniflorin Increases Prostaglandin-endoperoxide Synthase 2 to Reduce Inflammation and Inhibit Colon Cancer Tumor Growth
Yi Zhang, Cuixia Liu, Yiwei Fu, Ni Liu, Wang ZhouBackground
Paeoniflorin, a principal bioactive component of Paeoniae Alba, inhibits liver, gastric, and lung cancers, but its precise role in colon cancer remains unclear.
Objectives
To explore the mechanism by which paeoniflorin inhibits colon cancer cell growth by regulating phosphoinositide 3-kinases–protein kinase B (PI3K–AKT) pathway and prostaglandin-endoper-oxide synthase 2 (PTGS2).
Materials and Methods
With 10 rats in the control group, another 40 rats were induced to develop a model of colon cancer, and they were divided into four groups: model group, PI3K–AKT inhibitor group, low-dose and high-dose paeoniflorin group. After treatment, the colon tissues were stained to observe the pathological change, and the Transwell chamber method and flow cytometry assessed the migration ability and apoptosis rate of colon cancer cells. Interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels were detected using enzyme-linked immunosorbent assay (ELISA), and reverse transcription quantitative polymerase chain reaction (RT-qPCR) determined the levels of PI3K, AKT, and prostaglandin-endoperoxide synthase 2 (PTGS2).
Results
Compared with healthy tissues in the control group, a tumor mass appeared in the model group, and the tumor in the PI3K–AKT inhibitor group was even larger than the model group, while the tumor was smaller in the compared paeoniflorin groups, especially the high-dose group. Importantly, PI3K–AKT inhibitor treatment elevated the number of invaded and migrated cells, while paeoniflorin treatment importantly suppressed colon cancer cell migration. PI3K–AKT pathway activity and the concentration of paeoniflorin can affect the apoptosis of colon cancer cells. Inhibiting the pathway decreased the apoptosis rate, while the addition of paeoniflorin dose-dependently induced apoptosis. Moreover, inhibition of PI3K–AKT resulted in an enhancement in IL-6 and TNF-α, but the contents were decreased in the presence of paeoniflorin. Paeoniflorin increased the expression of PI3K and AKT, as well as up-regulated PTGS2 expression; PI3K–AKT inhibitors decreased the expression of PI3K, AKT, and PTGS2.
Conclusion
Paeoniflorin decreases PI3K–AKT activity and promotes the expression of PTGS2 to attenuate inflammatory response, thereby inhibiting the proliferation of colon cancer tumors. Therefore, paeoniflorin may become a new medicinal material for colon cancer treatment.