Effect of ursolic acid combined with gemcitabine on proliferation and apoptosis of pancreatic cancer PANC-1 cells / 中国肿瘤生物治疗杂志

ABSTRACT

@#[Abstract] Objective: To study the effects of ursolic acid cooperated with gemcitabine on proliferation and apoptosis of pancreatic cancer PANC-1 cells. Methods: Human pancreatic cancer cell line PANC-1 was cultured in vitro with ursolic acid and gemcitabine respectively; and MTT assay was used to determine the IC50 of ursolic acid and gemcitabine, thus obtaining the best drug concentration. Ursolic acid (2 µmol/L) and gemcitabine (0.2 µmol/L) alone or in combination was used to treat PANC-1 cells; trypan blue assay was used to test cell viability, and PI staining was used to examine the cell apoptosis; wound healing was used to detect the proliferation and migration of PANC-1 cells. The protein expressions of P-JNK, Bcl-2, IL-6, P-Stat 3, NF-κB and Cox-2 in cells of each treatment group were detected using Western blotting. Results: Both ursolic acid and gemcitabine could significantly inhibit the proliferation of PANC-1 cells, and the IC50 is 13.67 and 2.78 µmol/L, respectively; and the final concentrations were determined at 2 and 0.2 µmol/L for ursolic acid and gemcitabine, respectively. Compared with single drug treatment, the combined treatment exerted a more prominent cell proliferation inhibition effect ([46.47±5.07]% vs [78.38±8.65]%, [76.12±3.23]%, all P<0.05), apoptosis-induction effect ([39.78± 7.01]% vs [20.35±8.51]%, [20.35±8.51]%, all P<0.01) and migration inhibition effect (P<0.01) on PANC-1 cells. Western blotting showed that the combined treatment strongly inhibited Bcl-2 and IL-6 expression, accelerated P-JNK protein expression compared with single drug treatment. Conclusion: The synergistic effect of ursolic acid and gemcitabine enhanced the inhibition on proliferation, migration, and promoted cell apoptosis of human pancreatic cancer cell line PANC-1, the mechanism may be associated with inhibition of Bcl-2, Il-6, P-stat 3 proteins and promotion of P-JNK protein.