Inhibition of Oleanolic Acid on Growth and Inflammatory Response in Colorectal Cancer Transplanted Tumors in Mice Based on SHH/GLI-1 Signaling Pathway
Objective:To explore effects of oleanolic acid (OA) on tumor growth and inflammatory response in colorectal cancer transplanted tumors in mice based on SHH/GLI-1 signaling pathway. Methods:A total of twelve SPF grade 6-week-old male BALB/c nude mice were subcutaneously injected with HT-29 cells to establish a colorectal cancer transplant tumor mouse model,and randomly divided into control group and intervention group,with 6 mice in each group. The intervention group received intraperitoneal injection of OA solution at a dose of 12.5 mg/(kg·d),while the control group received intraperitoneal injection of physiological saline at a dose of 20 mL/(kg·d). The treatment lasted for 6 days and was stopped for 1 day,for a total of 16 days. During the intervention period,the body mass and tumor volume of mice were measured every 2 days,while tumor weight was measured after the intervention. Immuno-histochemistry was used to detect the expression of tumor tissue proliferation markers Ki67,cycle-associated proteins[cyclin depen-dent kinase inhibitor (p21),cyclin dependent kinase 4 (CDK4),Cyclin D1],apoptosis-associated proteins[B-cell lymphoma-2 (Bcl-2),Bcl-2 associated X protein (Bax),phosphorylated Bcl-2 antagonist of cell death (p-Bad),death factor (Fas),death factor ligand (FasL)],inflammation-associated proteins[cyclooxygenase-2 (COX-2),nitric oxide synthase (iNOS)]and the expression of SHH/GLI-1 signaling pathway associated proteins[Sonic hedgehog (SHH),patch receptor (PTCH),smooth protein (SMO),glioma associated oncogene homolog 1 (GLI-1)]. TUNEL method was used to detect the apoptosis of tumor cells. Bio plex was used to detect the expres-sion of inflammatory factors interleukin (IL)-1β,IL-6,tumor necrosis factor-α (TNF-α) in the serum of the two groups of mice. Re-sults:There was no significant difference in body weight between the two groups at different time periods (P>0.05). Compared with the control group,the tumor volume in mice at 7,9,11,13,15,17,and 19 days of intervention in the intervention group significantly decreased (P<0.05),while the tumor weight after intervention significantly decreased (P<0.05). Compared with the control group,the expression of Ki67,CDK4,Cyclin D1,Bcl-2,COX-2,iNOS,SHH,PTCH,SMO and GLI-1 in tumor tissue in the intervention group significantly decreased,as well as IL-1 β,IL-6,and TNF-α in serum (P<0.05),while the expression of p21,Bax,p-Bad,Fas and FasL in tumor tissue and the proportion of apoptotic cells significantly increased (P<0.05). Conclusion:OA can inhibit the growth and inflammatory responses of colorectal cancer transplanted tumors in mice,which may be related to the regulation of the SHH/GLI-1 signaling pathway.