Chinese Journal of Biochemistry and Molecular Biology. 2014, (07) Core

Inhibited PI3K Synergism with TRAIL to Induce Apoptosis in Breast Cancer MCF- 7 CellsChinese Full Text

ZHU Ming-Yue;LI Wei;XIA Hua;LU Yan;DONG Xu;CHEN Yi;GUO Jun-Li;FU Shi-Gan;XIE Xie-Ju;LI Meng-Sen;Agriculture College of Hainan University;Hainan Key Laboratory of Carcinogenesis and Intervention,Hainan Medical College;Key Laboratory of Molecular and Biology,Hainan Medical College;Department of Pathophysiology,Hainan Medical College;Tumor Institute of Hainan Medical College;

Abstract: Tumor necrosis factor-related apoptosis-inducing ligand（ TRAIL） is a member of the tumor necrosis factor（ TNF） superfamily and has been shown to induce extrinsic pathway of apoptosis in many types of cancer cells,but in breast cancer MCF-7 cell it displayed resistance to cytotoxicity of TRAIL.This investigation aim to study the effect of phosphatidylinositol 3-kinase（ PI3K） signal pathway on MCF-7 cells resisted the cytotoxicity of TRAIL. Human breast cancer MCF-7 cells were treated with TRAIL or Ly294002 alone /in combination. MTT cell viability assay was used to evaluate growth of the cells. For showing the change of morphology and nucleolus in MCF-7 cells,both microscopical photograph and 4,6-diamino-2-phenylindole（ DAPI） stained detects were performed. Flow cytometry was applied to analyze the apoptosis of the cells; Laser confocal microscopy was applied to observe location and migration of poly（ ADP-ribose） polymerase-1（ PARP-1） and Western blot analysis was conducted to evaluate DR4,DR5,DcR1,DcR2,caspase-3 /8,Src and pAKT（ Ser473） protein levels. The results indicated that sequential treatment of small dose of Ly294002（ !40 μmol /L） or TRAIL（ !80 nmol /L） had little suppressive impact on the growth,but Ly294002（ 80 μmol /L） or TRAIL（ 160 nmol /L） significant inhibited the proliferation of MCF-7 cells. Pretreated with Ly294002（ 20 μmol /L） followed treated with TRAIL（ 40 nmol /L）resulted in significant synergistic cytotoxicity and apoptosis,suggesting that MCF-7 cells were under strong apoptotic stimuli. Western blot assay showed that MCF-7 expressed DR4,DR5,DcR1,DcR2,caspase-8. Pretreatment of MCF-7 cells with Ly294002（ 20 μmol /L） and followed treat with TRAIL（ 40nmol /L） not only promoted PARP-1 to enter cytoblast,but also suppressed the expression of Src and pAKT（ Ser473） in the cancer cells. These findings strongly suggest that inhibition of PI3K /AKT signal enhances sensitivity of MCF-7 cells to TRAIL; MCF-7 cells resistance the apoptosis induced by TRAIL via activation of PI3K /AKT signal pathway to stimulate the expression of Src. These demonstrated that the results make Ly294002 and TRAIL a novel combination treatment candidate for breast cancer.

Keywords：

breast cancer cells; apoptosis; tumor necrosis factor-related apoptosis-inducing ligand（TRAIL）; PI3K signal pathway.;

DOI：
10.13865/j.cnki.cjbmb.2014.07.008
Series：
Subject：
Classification Code：
R737.9

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Inhibited PI3K Synergism with TRAIL to Induce Apoptosis in Breast Cancer MCF- 7 CellsChinese Full Text

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