Zhang J.,Zhejiang University |
Zhang D.,Hangzhou Cancer Hospital |
Wu G.-Q.,Zhejiang Provincial Peoples Hospital |
Feng Z.-Y.,Zhejiang University |
Zhu S.-M.,Zhejiang University
Hepatobiliary and Pancreatic Diseases International | Year: 2013
BACKGROUND: Propofol is one of the extensively and commonly used intravenous anesthetics and has the ability to influence the proliferation, motility, and invasiveness of many cancer cells. In this study, the effects of propofol on hepatocellular carcinoma cells invasion ability were examined. METHODS: We assessed the invasion ability of HepG2 cells in vitro by determining enzyme activity and protein expression of MMP-9 using gelatin zymography assay and Western blot. The real-time PCR was used to evaluate the effect of propofol on microRNA-199a (miR-199a) expression, and miR-199a-2 precursor to evaluate whether over-expression of miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed. RESULTS: Propofol significantly elevated the expression of miR-199a and inhibited the invasiveness of HepG2 cells. Propofol also efficiently decreased enzyme activity and protein expression of MMP-9. Moreover, the over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells. CONCLUSION: Propofol decreases hepatocellular carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a. © 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.
Jiang H.,Zhejiang Hospital |
Zhao P.-J.,Hangzhou Cancer Hospital |
Su D.,Cancer Institute |
Feng J.,Cancer Institute |
Ma S.-L.,Cancer Institute
Molecular Medicine Reports | Year: 2014
Polyphyllins, a major component of Rhizoma paridis, have been extensively used in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effects of Paris saponin I (PSI) on a panel of gefitinib-resistant NSCLC cell lines and its inhibition of tumor growth in a nude mouse model. The MTT assay was used to assess growth inhibition. The cell cycle was analyzed using flow cytometry and apoptosis was assessed using Annexin V/propidium iodide staining. The morphology of the apoptotic cells was determined by transmission electron microscopy. The protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 were detected using western blot analysis. In addition, the glucose metabolism in tumor-bearing mice was evaluated using 18F-fludeoxyglucose (FDG) micro-positron emission tomography imaging. The PSI-induced growth inhibition rate was observed to significantly increase in a time- and dose-dependent manner. Furthermore, PSI induced significant G2/M-phase arrest and apoptosis. The expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following PSI treatment. 18F-FDG-uptake in the PSI treatment groups was significantly decreased compared with that in the control group in vivo. In conclusion, PSI is a potent antitumor agent that acts by inhibiting the proliferation of gefitinib-resistant cells, and has potential as a candidate for a natural drug for gefitinib-resistant therapy. PSI-induced apoptosis, which occurred via multiple pathways, including G2/M-phase arrest and upregulation of the Bax/Bcl-2 ratio and caspase-3 expression, ultimately led to cell death and tumor inhibition.
Ni L.,Taizhou Central Hospital |
Liang X.,Hangzhou Cancer Hospital
Wspolczesna Onkologia | Year: 2014
Aim of the study: To evaluate the feasibility of whole-brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) by forward intensity-modulated radiation therapy (IMRT) in patients with 1-3 brain metastases. Material and methods: Two forward IMRT plans were implemented among 18 patients. In plan A, the prescribed dose was 30 Gy to the whole brain (PTVWBRT) and 50 Gy to individual brain metastases (PTVboost) delivered simultaneously in 10 fractions. In plan B, the prescribed dose was 30 Gy to the PTVWBRT and 40 Gy to the PTVboost. Plans were evaluated with regard to conformation number (CN), prescription isodose volume to target volume ratio (PITV), target coverage (TC), homogeneity index (HI), and the volume receiving at least 95% of the prescribed dose (V95). Plan A was implemented for 5 of these patients, and plan B was used for the remaining patients. Results: The mean values of CN, PITV, TC, and HI for the PTVboost were 0.71, 1.32, 0.97, and 0.07, respectively, for plan A and 0.65, 1.47, 0.97, and 0.05, respectively, for plan B. The mean values of TC, HI, and V95 for the PTVWBRT were 0.98, 0.45, and 99.71%, respectively, for plan A and 0.97, 0.27, and 99.61%, respectively, for plan B. All patients completed the planned radiotherapy (RT) schedule with no acute and late RT-related toxicity greater than grade 2. Conclusions: It is feasible to deliver WBRT with a SIB via forward IMRT for patients with 1-3 brain metastases with good dose conformity and acceptable toxicity.
Zhang H.,Hangzhou Cancer Institution |
Luo H.,Huaian First Peoples Hospital |
Hu Z.,Hangzhou Cancer Institution |
Peng J.,Huaian First Peoples Hospital |
And 8 more authors.
Oncotarget | Year: 2015
Radiotherapy is a primary treatment modality for esophageal squamous cell carcinoma (ESCC). However, most of patients benefited little from radiotherapy due to refractory radioresistance. We found that WISP1, a downstream target gene of Wnt/ß-catenin pathway, was re-expressed in 67.3 % of ESCC patients as an oncofetal gene. Expression of WISP1 predicted prognosis of ESCC patients treated with radiotherapy. Overall survival in WISP1-positive patients was significantly poorer than in WISP1-negative patients. Serum concentration of WISP1 after radiotherapy reversely correlated with relapse-free survival. Gain and loss of function studies confirmed that WISP1 mediated radioresistance both in esophageal squamous cancer cells and in xenograft tumor models. Further studies revealed that WISP1 contributed to radioresistance primarily by repressing irradiation-induced DNA damage and activating PI3K kinase. LncRNA BOKAS was up-regulated following radiation and promoted WISP1 expression and resultant radioresistance. Furthermore, WISP1 facilitated its own expression in response to radiation, creating a positive feedback loop and increased radioresistance. Our study revealed WISP1 as a potential target to overcome radioresistance in ESCC.
Zhao P.,Hangzhou Cancer Hospital |
Jiang H.,Zhejiang Hospital |
Ma S.,Hangzhou First Peoples Hospital |
Zhu X.,Zhejiang Hospital
Molecular Medicine Reports | Year: 2015
Rhizoma paridis is widely used for cancer therapy due to its potential involvement in the suppression of tumor growth. However, at present there is no clear explanation for the mechanism underlying the inhibitory effects of Rhizoma paridis combined with hyperthermia on tumor growth. The aim of the present study was to evaluate the effects of Paris saponin I (PSI) combined with hyperthermia on a variety of non-small cell lung cancer (NSCLC) cell lines. An MTT assay was used to determine the levels of growth inhibition. The cell cycle was analyzed using flow cytometry and cell apoptosis was analyzed with Annexin V/propidium iodide staining and the Hoechst assay. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase.3 proteins were detected using western blotting. The inhibition rates significantly increased with PSI in combination with hyperthermia at 43°C. PSI with hyperthermia at 43°C caused G2/M phase arrest and significantly induced apoptosis. The expression level of Bcl-2 decreased, while Bax expression increased following treatment with PSI with hyperthermia at 43°C. In addition, the protein expression of caspase-3 was significantly enhanced. PSI combined with hyperthermia is a potent antitumor treatment through the inhibition of proliferation of NSCLC cells and may be developed as a new antitumor therapy. PSI combined with hyperthermia significantly induced apoptosis through a multi regulatory process involving G2/M arrest and regulation of Bax, Bcl-2 and caspase-3 expression, resulting in cell death and tumor inhibition.