Effect of 5-lipoxygenase and 12-lipoxygenase on proliferation and apoptosis of pancreatic cancer cell / 中华消化杂志

ABSTRACT

Objective To examine the expression of lipoxygenases (LOXs)on human pancreatic carcinoma and their effects on proliferation and apoptosis of human pancreatic carcinoma in vitro.Methods Expression of 5- LOX and 12-LOX in the tissue of human pancreatic carcinoma and pancreatic cancer cell line (SW1990) was detected by immunohistochemical staining and RT-PCR.To examine the effects of polyunsaturated fatty acids on pancreatic cancer cell line,the proliferation rate of SW1990 cells treated with arachidouic acid (AA),docosahexaenoic acid (DHA) and eicosapentenoic acid (EPA) was analyzed by MTT and the incorporation of bromodeoxyuridine (BrdU) methods.An annexinV/propidium iodide (PI) assay with flow cytometry and in situ terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay were used to identify potential induction of apoptosis by the unsaturated fatty acids.The effects of 5-LOX inhibitor (MK-886) and 12-LOX inhibitor (baicalein) on the proliferation of SW1990 cells were determined by above methods.Results Both 5-LOX and 12-LOX were over expressed in the tissue of human pancreatic carcinoma and the pancreatic cancer cell line.AA had a stimulatory effect on the growth of SW1990 cells while EPA and DHA had an inhibitory effect in a dose-dependent manner.The apeptosis of SW1990 cells co-cultured with DHA or EPA lasting for 24 hours was increased markedly.Furthermore, both MK-886 and baicalein in a dose-dependent-manner inhibited the growth of SW1990 cells ard induced a significant increase of apoptotic cells rate.Conclusions Expression of lipoxygenase is up-regulated in human pancreatic cancer. Polyunsaturated fatty acids have regulatory effects on the growth of pancreatic carcinoma in vitro.AA stimulates proliferation of pancreatic cancer cell line,while DHA and EPA suppress proliferation,simultaneously inducing apoptosis of pancreatic cancer cell line.Blocking the functions of lipoxygenase with its inhibitor exerts a negative regulatory effect on the growth of pancreatic carcinoma in vitro.Lipoxygenase might be a novel therapeutic target for the pancreatic cancer.