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Dysregulation and Effect of Bim in Melanoma Cells in the State of ER Stress

Author: HouLiLi
Tutor: ZhangLinJie；ZhangXuDong
School: Anhui Medical University,
Course: Immunology
Keywords: Melanoma Apoptosis Bim Endoplasmic reticulum stress Small interfering RNA
CLC: R739.5
Type: Master's thesis
Year: 2011
Downloads: 25
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Abstract

BACKGROUND AND PURPOSE: many solid tumors, including melanoma acquired tolerance to therapy, or in the case of repeated treatment tolerance become a major obstacle to the clinical treatment, this is largely due to the tumor cells to chemotherapeutic drug-induced apoptosis not sensitive. The present study show that in addition to the death receptor and the mitochondrial pathway, the endoplasmic reticulum also plays an important role in the regulation of the chemotherapy drug-induced apoptosis. Some chemotherapy drugs can cause endoplasmic reticulum stress and the unfolded protein response in the endoplasmic reticulum stress and protect cells by slowing the endoplasmic reticulum stress, but too strong or duration too long stress response can cause apoptosis. Recent research results show that: melanoma endoplasmic reticulum stress-induced apoptosis is not sensitive to the anti-apoptotic mechanism is not yet completely clear. But play an important regulatory role has been clearly and closely related to the mitochondrial pathway BH3-only family proteins endoplasmic reticulum stress-induced apoptosis, which upregulated Bim in the endoplasmic reticulum stress apoptosis-sensitive cells and play an important pro-apoptotic role, but Bim expression in melanoma cells under endoplasmic reticulum stress state are poorly understood, this project aims to investigate the regulation of endoplasmic reticulum stress state Bim in melanoma cells, as well as its role in melanoma cell endoplasmic reticulum stress apoptosis tolerated chemotherapy-induced apoptosis in melanoma is not sensitive to the molecular mechanism more perfect. Methods: processing melanoma MEL-RM cell lines using the natural nucleosides antibiotic tunicamycin (TM), HEK293 cells strains MM200 cell lines and the control group, the establishment of the model of the endoplasmic reticulum stress. Annexin Ⅴ / PI double staining and Hoechst staining to detect apoptosis by flow cytometry technique (FCM); protein level; Western blot detection of caspase-3, -9 and PARP activation and Bim, GRP78, CHOP and FOXO1 such as real-time fluorescence Quantitative PCR detection of Bim, CHOP and of FOXO1 the mRNA level; small interfering RNA (siRNA) technology-specific \cytometry detection of \Results: TM role melanoma cells and HEK293 cells, two cells to drug-induced apoptosis in a dose-and time-dependent manner, but melanoma cells than HEK293 cells compared to the endoplasmic reticulum stress apoptosis performance tolerated. HEK293 cells in the control group, caspase-3, -9 significantly activated, but not in melanoma cells. Including melanoma cells under endoplasmic reticulum stress state of Bim protein levels did not increase the mRNA level down. Detection of melanoma cells in the endoplasmic reticulum stress regulation of Bim expression levels of the transcription factor CHOP raised, another transcription factor FOXO1 expression levels down. TM induced HEK293 cells specific \Conclusion: the melanoma cells of Bim endoplasmic reticulum stress state are improperly regulated, which may be related to the transcription factor CHOP and FOXO1 this abnormal regulation may lead to the endoplasmic reticulum stress-induced apoptosis of melanoma cells resistant by important reason, therefore Bim is to improve melanoma endoplasmic reticulum stress apoptotic sensitivity of an important target.

Dysregulation and Effect of Bim in Melanoma Cells in the State of ER Stress

Abstract

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