URSOLIC ACID INHIBITS PROLIFERATION OF ESOPHAGEAL CANCER CELL BY REGULATING BCL-2, BAX AND P27KIP1 EXPRESSION

Sihui Zhang^*, Gaohua Han, Yunyao Ye

Department of Oncology, The Fifth Affiliated Hospital of Nantong University, Taizhou People's Hospital, Taizhou 225300, PR China

Objective: To investigate the mechanism of ursolic acid (UA) inhibiting the proliferation of esophageal cancer cells by regulating Bcl-2, Bax and P27kip1 expression.

Methods: The human esophageal cancer cell lines Eca-109 were selected, randomly divided into a blank control group, a UA low concentration group, a UA medium concentration group and a UA high concentration group. The cells in the control group did not receive any treatment. The cells in the UA low concentration group, UA medium concentration group and UA high concentration group were treated with 30 μmol/L, 40 μmol/L and 50 μmol/L UA, respectively, and then cells in the logarithmic growth period were used for the experiment. The apoptosis ability, cell cycle distribution (G₀/G₁ phase, S phase, G2/M phase), Bcl-2, Bax and P27^kip1 protein expression level and cell proliferation ability (OD value and proliferation inhibition rate) of human esophageal cancer cell line Eca-109 were compared.

Results: The OD values of the UA concentration groups were significantly lower than those of the blank control group, and the proliferation inhibition rate was remarkably higher than that of the blank control group, and both were time and concentration dependent (P<0.05). In the fluorescence staining assay of the blank control group, the color of the cell nucleus was uniform and light. In the UA concentration groups, the cell nucleus was not uniformly colored, the color was dark, and the samples were bright blue and showed nuclear shrinkage, with small ruptures. In addition, granular hyperchromatic substances appeared, and there was significant evidence of promoted apoptosis. The apoptosis rates of the UA concentration groups were markedly higher than that of the blank control group, and they were time and concentration dependent (P<0.05). The cell distribution in the G₀/G₁ phase of the UA concentration groups was significantly higher than that of the blank control group, and the cell distribution in the S and G₂/M phases was dramatically lower than that of the blank control group, and it was concentration dependent (P<0.05). The expression of P27^kip1 and Bax protein in the UA concentration groups was remarkably higher than that in the blank control group. The expression level of Bcl-2 protein was significantly lower than that in the blank control group and showed a concentration dependence (P<0.05).

Conclusion: Ursolic acid can promote the apoptosis of esophageal cancer cells and hinder cell proliferation, and its mechanism may be achieved by enhancing Bax expression, weakening Bcl-2 expression and increasing P27kip1 expression to block cells at the G₀/G₁ phase.