Sulindac Inhibits Human Pancreatic Cancer Cells Prolifiration By Targeting Survivin/Aurora B/Op18 Pathway

BACKROUND & AIM: Recently non-steroidal anti-inflammatory drugs had been recognised that them have obvious anti-tumoral effects on many kinds of human cancer cells, but its mechanisms are still not explained thoroughly. Both survivin and Aurora B are the members of the chromosomal passenger complex . They play important roles in chromosome alighment, spindle assembly and the following cytokinesis. They also activate each other. The breakdown of their relationships leads to decrease of the function of CPC upon mitosis. Op18 is a conservative phosphoprotein that was firstly found in leukemic cell. It is integrated with tubulin and then influences microtubule dynamics by promoting disassembly of microtubules. Its phosphorylation is retulated ba Aurora B and could be a maker of the activity of Aurora B. Here we observe the expression of survivin, Aurora B and Op18 at the transcription and protein level, the changes of cell cycle and cell proliferation after the action of sulindac, expolre their relationships and make sure if proliferation in human pancreatic cancer cells is blocked through this pathway.METHODS: MTT assay was used to determine the influence of sulindac on the proliferation of the cells; RT-PCR was used to detect mRNA level of survivin, Aurora B and Op18 after using different concentrations of sulindac; western blot was used to detect protein expression of survivin, Pho-Aurora B Thr-232 and Pho-Op18 Ser-16; the cell cycle was detected by flow cytometry.RESULTS: The BXPC-3 cells were obviously inhibited by sulindac in dose and time-dependent manner;after the incubation of sulindac with the concentration of 500μmol/L, the expression of mRNA of survivin, Aurora B and Op18 were all significantly decreased; the expression of survivin protein and the phosphorylation of Aurora B Thr-232 and Op18 Ser-16 were also decreased; the proportion of cells in the G0/G1 phase was increased at (70.58±3.21)%, and the proportion in the S phase of cell cycle was decreased at (14.73±2.10)%.CONCLUSION: Sulindac has inhibitory effects on the growth of BXPC-3 cells, the possible mechanism is that sulindac decreases the expression of survivin and the activity of Aurora B and Op18, then the CPC′role in chromosome and alighment cytokinesis is influenced. The most of the cells were blocked in the G0/G1 phase, at last the cells'proliferation were inhibited.