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@#[Abstract] Objective: To observe the effects of shikonin on the proliferation, apoptosis and cell cycle of human esophageal carcinoma TE-1 cells, and to explore its mechanism. Methods: TE-1 cells were treated with different concentrations of shikonin (0, 1, 5, 10 µmol/L). MTT assay was used to detect cell proliferation at different time points (24, 48 and 72 h). After treatment with shikonin for 48 h, cell apoptosis in TE-1 cells of each group was observed with Hoechst 33258 fluorescence staining. Flow cytometry was used to detect apoptosis and cell cycle. The changes in expression of TRAP1/Akt/mTOR signaling pathway related proteins were detected by Western blotting. Results: Shikonin inhibited the proliferation of TE-1 cells in a time-dose-dependent manner (P<0.05 or P<0.01). Compared with the control group, shikonin significantly promoted the apoptosis of TE-1 cells (P<0.01), induced the G0/G1 phase block of TE-1 cells (P<0.05 or P<0.01), and reduced the expression levels of TRAP1, p-Akt and p-MTOR (P<0.05 or P<0.01). The above effects were all dose-dependent. Conclusion: Shikonin can significantly inhibit the proliferation of TE-1 cells in vitro, induce G0/G1 phase arrest and promote apoptosis, which may be closely related to the inhibition of TRAP1/Akt/mTOR signaling pathway.
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Objective The aim of this study was to investigate the role and mechanism of tumor necrosis factor receptor-re-lated protein 1(TRAP1)in the progression of human esophageal cancer. Methods Immunohistochemistry was used to detect the ex-pression of TRAP1 and S100A8 in human esophageal cancer tissues. A stably knocked-down TRAP1 cell line was established in the esophageal cancer KYSE150 cell line,the proliferation ability was detected by CCK-8,the transfer ability was detected by Transwell, and apoptosis was detected by flow cytometry. We conducted a gene profiling study to detect the expression of genes related to tumor progression. The expression of TRAP1 downstream genes-E-Cadherin,N-Cadherin and S100A8 was detected by Real-Time fluo-rescent quantitative PCR. Results The expression of TRAP1 in esophageal carcinoma was significantly higher than that in adjacent tissues and correlated with S100A8(χ2=4. 141,P<0. 001). The KYSE150 cell line with down-regulated of TRAP1(KYSE150-TRAP1)was established,and the expression of TRAP1 was down-regulated by 85% ,cell invaded ability was decreased by 46% ,no changes of cell proliferation and apoptosis were observed,when compared to the KYSE150 control cells. The expression level of E-cadherin was increased by 19% ,and the expression level of S100A8 was decreased by 39% in KYSE150-TRAP1 cells. Conclusion TRAP1 is overexpressed in esophageal carcinoma and promotes the metastasis of esophageal carcinoma by regulating S100A8 ex-pression.
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Tumor necrosis factor receptor-associated protein 1(TRAP1),also known as HSP75,is a molecular chaperone protein of heat shock protein 90(HSP90)which can be expressed in a variety of human malignant tumor cells.TRAP1 is involved in cell apoptosis,metabolism,intercellular adhesion,movement,invasion and metastasis,and is associated with tumor cell resistance.The latest studies have demonstrated that abnormal expression of TRAP1 was found in the development process of breast cancer,colon cancer,ovarian cancer and other tumors.Further studies have confirmed that TRAP1 plays a key role in the regulation of energy metabolism in tumor cells,by blocking its function can lead to the death of tumor cells,and will not affect the normal cells.As a new target for tumor therapy,TRAP1 is receiving more and more attention.
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Purpose To investigate TRAP1 expression in esophageal cancer and its relationship with clinicopathological features and prognosis.Methods Expression levels of TRAP1 in 60 pairs of cancer and adjacent normal tissues were detected by immunohistochemistry,and the relevance between TRAP1 and clinicopathological features was evaluated.Kaplan-Meier and Cox proportional regression analyses were performed to determine the association of TRAP 1 expression and survival of the patients.Results The positive expression rate of TRAP1 was 55.0％,and the amount of relative protein transcript level was 2.7 ± 1.1 in the cancer tissue.The positive expression rate of TRAP1 was 11.7％,and the relative expression protein was 0.5 ± 0.4 in the adjacent normal tissue.The expression level of TRAP1 in cancerous tissue was significantly higher than that of tissue adjacent to carcinoma.There was no statistically significant difference between the expression levels of TRAP1 with sex,age,location,and degree of differentiation (P ＞ 0.05).There was statistically significant relationship between recurrence,metastasis and TNM stages with the expression of TRAP1 levels (P ＜ 0.05).The average survival time of TRAP1-negative patients was 69.0 months (95％ CI:60.2-77.9) while the TRAP1-positive patients was 34.2 months (95％ CI:24.4-44.1).High levels of TRAP1 were correlated with decreased survival of postoperative esophageal cancer patients (P ＜ 0.05).Conclusion TRAP1 is overexpressed in esophageal cancer and associated with the progression and prognosis of esophageal cancer.
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Objective:To investigate the effect and related mechanism of TRAP1 on the invasion and migration of human bladder cancer through TGF/Smad3 signal path.Methods: Selected from BIU-87 of high expression of TRAP1 in bladder cancer cell lines through Western blot techniques.TRAP1 knockdown lentivirus (LV3-TRAP1) was used to silence the expression of TRAP1.GFP fluorescene and PCR detector was used to detected the efficiency of gene silencing and the effectiveness of gene silencing;effect of TRAP1 on the invasion and migration ability of BIU-87 were detected by Transwell matrigel invasion assays and wound healing assays,CM-H2DCFDA fluorescent staining was used to deteced the cell ROS of BIU-87 with LV3-TRAP1.Detected the level of TGF/Smad3 signal protein by Western blot.Results: LV3-TRAP1 lentivirus could effectively inhibit the expression of TRAP1 compared with LV3-NC.LV3-TRAP1 lentivirus could effectively inhibit the cell RPS of BIU-87.Knockdown the expression of TRAP1 could inhibit the invasion and migration of BIU-87.Knockdown the expression of TRAP1 in BIU-87 could reduce the protein level of TGF/Smad3.Conclusion: Silencing TRAP1 could inhibit the invasion and migration of bladder cancer cell through TGF/Smad3 signal pathway.
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Tumor necrosis factor receptor-associated protein 1 (TRAP1),as one of the main members of the heat shock protein 90 family, resists oxidative stress-induced apoptosis as well as predominantly maintains the integrity of mitochondria and cellu-lar homeostasis. Abnormal expression of TRAP1 was herein closely related to the onset and progression of a wide variety of tumors. As a key regulatory factor mediating energy metabolism within tumor cells, TRAP1 may be able to kill them by interfer-ing with such metabolism. More importantly, the abnormal ex-pression of TRAP1 played a less important role in normal cells, allowing TRAP1 to be a particularly attractive target as it can be used in tumor treatment or interference. The relationship be-tween abnormal expression of TRAP1 protein and tumor onset was reviewed. Besides, the mechanism by which disordered TRAP1 protein expression induced tumor formation was postula-ted, which may provide references for future research and clini-cal treatment.
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PURPOSE: The novel heat shock protein tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with multidrug resistance in colorectal cancer (CRC) cells in vitro. Excision repair cross-complementation group 1 (ERCC1) expression levels in tumor tissues also predict clinical outcomes in metastatic CRC patients receiving combination oxaliplatin and 5-fluorouracil treatment. We investigated whether TRAP1 and ERCC1 protein expression by immunohistochemistry predict clinical outcomes in CRC patients. MATERIALS AND METHODS: The study population consisted of 56 patients with metastatic CRC who received first-line oxaliplatin/5-fluorouracil therapy. Clinical response and overall survival (OS) by levels of the markers TRAP1 and ERCC1 were evaluated. RESULTS: The rates of TRAP1 and ERCC1 expression were 21% and 52%, respectively. Patients negative for ERCC1 expression showed a tendency to respond to chemotherapy (p=0.066). Median OS was significantly longer in patients negative for TRAP1 than those positive for TRAP1 (p=0.023). Patients negative for ERCC1 expression also had a better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9 months for patients negative for TRAP1 and ERCC1 compared to 13.2 months for those positive for TRAP1 and/or positive for ERCC1 expression (p=0.006). The combination of TRAP1 and ERCC1 expression was significantly associated with the response to chemotherapy (p=0.046) and independently predicted median OS in multivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49). CONCLUSION: The present study demonstrates that the combination of TRAP1 and ERCC1 expression predicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.
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Humans , Colorectal Neoplasms , DNA Repair , Drug Resistance, Multiple , Drug Therapy , Fluorouracil , Heat-Shock Proteins , Immunohistochemistry , Multivariate Analysis , Tumor Necrosis Factor-alphaABSTRACT
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Most cases are sporadic and its etiology is incompletely understood. However, increasing evidence suggests that oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of Parkinson's disease. The aim of this study was to investigate changes in mitochondrial protein profiles during dopaminergic neuronal cell death using two-dimensional gel electrophoresis in conjunction with mass spectrometry. Several protein spots were found to be significantly altered following treatment of MN9D dopaminergic neuronal cells with 6-hydroxydopamine (6-OHDA). Among several identified candidates, TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone, was released from the mitochondria into the cytosol in MN9D cells as well as primary cultures of dopaminergic neurons following 6-OHDA treatment. This event was drug-specific in that such apoptotic inducers as staurosporine and etoposide did not cause translocation of TRAP1 into the cytosol. To our knowledge, the present study is the first to demonstrate the drug-induced subcellular translocation of TRAP1 during neurodegeneration. Further studies delineating cellular mechanism associated with this phenomenon and its functional consequence may provide better understanding of dopaminergic neurodegeneration that underlies PD pathogenesis.