Jing Zhang*, **, Xiao-ping Tan**, Yan Zhang**, Xiao-wei Qi*, Gui Qi*, Qing Zhang**
*Yangtze University Health Science Center, No.1, Nanhuan Road, Jingzhou District, Jingzhou City, Hubei Province, China - **Department of Gastroenterology, No. 1 Hospital Affiliated to Yangtze University, No.8, Hangkong Road, Shashi District, Jingzhou City, Hubei Province, China
Objective: To investigate the effect of ursolic acid combined with oxaliplatin in inhibiting cell growth in rectal cancer and the possible mechanism.
Methods: Human rectal cancer cell line SW480 was cultured in vitro, and all cells were divided into control group (with culture solution only), ursolic acid group (45 µmol/L ursolic acid treatment), oxaliplatin group (10mg/L oxaliplatin treatment) and combination group (45 µmol/L ursolic acid +10mg/L oxaliplatin treatment). The changes of cytological morphology after drug treatment were observed under inverted microscope. The change of cell proliferation level was detected by MTT colorimetry. The changes of cell cycle and apoptosis rate were detected by flow cytometry. The protein expressions of Bax and Bcl-2 were detected by Western blot.
Results: The number of cells in ursolic acid group and oxaliplatin group decreased, the morphology became round, and the growth was inhibited. The cytoplasm of the combined drug group showed shrinkage and vacuole, and many cells ruptured. The results of MTT colorimetric assay showed that compared with the control group, the ursolic acid group treated with SW480 cells showed obvious inhibition of cells (P<0.05), and the oxaliplatin group showed obvious cell inhibition after treatment for 24 hours. (P<0.05), the inhibition was significantly higher after 48h compared with the control group (P<0.01), and the combination group showed extremely significant cell inhibition after treatment for 24h (P<0.01). The results of flow cytometry showed that compared with the control group, the percentage and apoptosis rate of G1/G0 phase cells in other groups were significantly increased (P<0.05), and the percentage of S phase and G2/M phase were significantly reduced (P<0.05).Western blot results showed that compared with the control group, the expression of Bax protein and Bcl-2 protein in tumor cells of other drug treatment groups was significantly increased and significantly decreased (P<0.05).
Conclusion: Ursolic acid combined with oxaliplatin can significantly inhibit the proliferation of rectal cancer cells, induce cell cycle arrest and promote apoptosis, and the mechanism may be related to the regulation of Bcl-2 and Bax protein expression.
Ursolic acid, Oxaliplatin, Rectal cancer, Proliferation, Mechanism of action.