15-PGDH诱导药物对人乳腺癌MCF-7细胞的生长抑制作用及其机制研究

Inhibitory Effect of 15-PGDH Induction Drugs on Growth of Human Breast Cancer MCF-7 Cells and Its Mechanism

目的探讨15-羟前列腺素脱氢酶(15-PGDH)诱导药物对人乳腺癌MCF-7细胞的生长抑制作用及其机制。方法采用MTT法测定4种非特异性15-PGDH诱导药物--布洛芬(IBU)、吲哚美辛(IND)、吡格列酮(PIO)、地塞米松(DXM)对MCF-7细胞增殖的影响;Hoechst 33258检测细胞凋亡情况;Western blotting检测15-PGDH、COX-2蛋白表达水平;ELISA法检测细胞上清液中PGE2水平。结果低毒浓度(IBU 200μmol·L^-1,IND 100μmol·L^-1,PIO 20μmol·L^-1,DXM 100 nmol·L^-1)下,4种15-PGDH诱导药物联合用药可协同增强阿霉素(ADM)、紫杉醇(TAXOL)对MCF-7细胞的生长抑制作用和凋亡诱导作用;4种15-PGDH诱导药物干预后,均可降低MCF-7细胞中COX-2蛋白表达水平和细胞上清液中PGE2水平,IBU可显著降低15-PGDH蛋白表达水平,而IND、PIO和DXM对15-PGDH蛋白表达无显著影响。结论15-PGDH诱导药物可增强ADM、TAXOL对MCF-7细胞的生长抑制作用和凋亡诱导作用,其机制可能与抑制COX-2表达、降低PGE2水平有关。

Objective To explore the inhibitory effect of 15-hydroxyprostaglandin dehydrogenase(15-PGDH)induction drugs on the groMh of human breast cancer MCF-7 cells and its mechanism.Methods Inhibitory effect of 15-PG DH induction drugs including ibuprofen(IBU),indomethacin(IND),pioglitazone(PIO)and dexamethasone(DXM)on breast cancer MCF-7 cells were assayed by MTT method.Cell apoptosis was detected by Hoechst 33258 stain assay.The 15-PGDH and COX-2 protein expressions in MCF-7 cells were detected by Western blotting.The prostaglandin E2(PGE2)levels in supernatant of cells were determined by ELISA assay.Results The four 15-PGDH induction drugs(IBU 200μmol·L^-1,IND 100μmol·L^-1,PIO 20μmol·L^-1,DXM 100 nmol·L^-1)enhanced the effects of proliferation-inhibition and apoptosis-induction when combined with doxorubicin(ADM)and paclitaxel(TAXOL)in MCF-7 cells.The expression of COX-2 protein and the level of PGE2 in the supernatant of MCF-7 cells were decreased after intenvention of the four 15-PGDH induction drugs.IBU could significantly reduce the expression of 15-PGDH protein,while the other three induction drugs had no effects on it.Conclusion 15-PGDH induction drugs could enhance the growth-inhibiting and apoptosis-inducing effects of ADM and TAXOL on MCF-7 cells.The mechanism might be related to the inhibition of COX-2 protein expression and the decrease of PGE2 level.