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Cao Z.,Breast | Zeng Q.,The Inner Mongolia Autonomous Region Peoples Hospital | Pei H.,Breast
Oncology Letters | Year: 2016

It is well known that heat shock protein 90 (HSP90) overexpression is correlated with poor prognosis and chemo‑resistance in human malignant cancers. At the same time, wighteone, or 6‑prenyl‑5,7,4'‑trihydroxyisoflavone, a major isoflavone component of the ornamental tall tree Erythrina suberosa, has been demonstrated to exhibit a potent anti‑proliferative effect on human leukemia HL‑60 cancer cell lines. In this study, the effects of wighteone on the proliferation of HER2‑positive breast cancer cells were investigated, and the action mechanism was explored. MCF‑7 HER2‑positive breast cancer cells were treated with various concentrations of wigh­teone. The growth inhibitory rate of the cells was calculated by MTT assay, apoptosis was detected by flow cytometry, and the expression level of HSP90 was assessed by western blot analysis. The addition of wighteone at concentrations ranging from 1‑10 g/ml in the medium for 48 h had a marked inhibi­tion on the proliferation of HER2‑positive cancer cell lines. The growth inhibitory rates with 0.5, 2 or 8 mM wighteone were significantly higher compared with the control group. Apoptosis in the wighteone‑treated cells was also significantly higher compared with the control group. The expression level of HSP90 in the wighteone group was significantly lower than that in the control group. Our findings demonstrated that wigh­teone effectively inhibited the proliferation of HER2‑positive cancer cell lines, and this is considered to be the result of downregulating HSP90 receptor and downstream signaling. © 2016, Oncology Letters. All rights reserved.

Lin X.,Chongqing Medical University | Zhou X.,Chongqing Medical University | Liu D.,Chongqing Medical University | Yun L.,The Inner Mongolia Autonomous Region Peoples Hospital | And 4 more authors.
In Vitro Cellular and Developmental Biology - Animal | Year: 2016

Hyperglycemia or high-glucose (HG)-induced apoptosis in human retinal pigment epithelial (RPE) cells is a characteristic process in diabetic retinopathy. In our study, we examined whether microRNA-29 (miR-29) may regulate HG-induced RPE cell apoptosis. Human RPE cell line, ARPE-19 cells, was treated with various high concentration of glucose in vitro. HG-induced RPE cell apoptosis was examined by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay and miR-29 gene expression by quantitative RT-PCR (qRT-PCR). miR-29 was then downregulated in RPE cells, and its effect on HG-induced apoptosis was examined by TUNEL assay and western blot assay on caspase-7 protein. Association of miR-29 on its downstream target, PTEN, in HG-induced RPE cell apoptosis was evaluated by dual-luciferase assay and qRT-PCR. PTEN was silenced in RPE cells. The effects of PTEN downregulation on miR-29-mediated HG-induced RPE cell apoptosis were also examined by TUNEL and western blot assays. HG induced significant apoptosis in RPE cells in a dose-dependent manner. miR-29 was upregulated by HG in RPE cells. miR-29 downregulation protected HG-induced apoptosis and reduced the production of caspase-7 protein in RPE cells. PTEN was shown to be directly downregulated by HG and then upregulated by miR-29 downregulation in RPE cells. Small interfering RNA (siRNA)-mediated PTEN downregulation reversed the protective effect of miR-29 downregulation on HG-induced RPE cell apoptosis. This study demonstrates that miR-29, through inverse association of PTEN, plays an important role in the process of HG-induced apoptosis in RPE cells. © 2016 The Society for In Vitro Biology

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