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Liang Y.,Tianjin Medical University | Guo S.,Jiangxi Provincial Cancer Hospital | Zhou Q.,Tianjin Medical University
Tumor Biology | Year: 2014

The prognostic value of matrix metalloproteinase-7 (MMP-7) for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. We performed a meta-analysis of the literatures to clarify its impact. Trials were selected for meta-analysis if they provided an independent assessment of MMP-7 in NSCLC and reported the analysis of survival data based on MMP-7 status. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to evaluate the associations between MMP-7 expression and survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Seven studies involving 1,446 patients were identified. The combined HR for all studies was 1.28 (95 % CI 0.86-1.91; P = 0.22). Subgroup analysis revealed that MMP-7 overexpression had a favorable impact on survival in Caucasians (HR = 0.74; 95 % CI 0.55-0.99; P = 0.043) but showed a poor survival prognosis in Asians (HR = 1.74; 95 % CI 1.05-2.88, P = 0.031). Its effect also appeared significant when the analysis was restricted to Asian patients with squamous cell cancer (HR = 3.42; 95 % CI 1.92-6.11, P = 0.000) and adenocarcinoma (HR = 2.1; 95 % CI 1.34-3.29, P = 0.001). Our meta-analysis suggests that there are ethnic differences in the clinical significance of MMP-7 expression for patients with NSCLC. © 2013 International Society of Oncology and BioMarkers (ISOBM).

Ji Y.,Fudan University | Cai L.,Fudan University | Zheng T.,Fudan University | Ye H.,Fudan University | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2014

Cataract is the most common eye disease that causes blindness in patients. Ultraviolet B (UVB) irradiation is considered an important factor leading to cataract by inducing apoptosis in human lens epithelial cells (HLECs), but the mechanism is currently unclear. In this study, we investigated HLECs under different intensities of UVB irradiation and different exposure time. The annexin V-FITC/propidium iodide staining results showed that UVB irradiation could efficiently lead to HLECs apoptosis in time- and dose-dependent manner. The expression of pro-apoptotic Bax gene was promoted by UVB irradiation, while anti-apoptotic Bcl-2 gene expression was inhibited at both transcript and protein levels. Notably, the ratio of Bax/Bcl-2 displayed a high and positive correlation to the proportion of apoptotic HLECs. Mitochondrial dysfunction was also observed with rapid loss of potential (∆Ψm), as well as changes of the levels of reactive oxygen species, malondialdehyde, total antioxidative capabilities, and superoxide dismutase. In caspase pathway, the level of caspase-3 protein increased after UVB irradiation. All these discovered changes may play important roles in UVB-induced HLECs apoptosis, and would be helpful in understanding the mechanism of UVB-induced cataract and providing potential prevention and treatment strategies. © 2014, Springer Science+Business Media New York.

He W.-X.,Guangxi Medical University | Huang C.-S.,Jiangxi Provincial Cancer Hospital | Quan J.-L.,Guangxi Medical University | Wu S.-M.,Guangxi Medical University | And 2 more authors.
Chinese Journal of Cancer Prevention and Treatment | Year: 2015

OBJECTIVE: To determine the effect of TG2 (transglutaminase type 2) on breast cancer cell invasion and metastasis, and to explore its function in the mechanism of breast cancer. METHODS: To knock down TGM2 (TG2 gene), an antisense construct (TG2 gene-specific lentiviral RNA interference vetor, TGM2-RNAi-LV) was designed, synthesized and stably transfected into MDA-MB-231 cell lines. The MDA-MB-231 cells were divided into three groups: the TGM2-RNAi group (RNAi group), the negative control group (NC group) and the blank control group (Con group). TGM2 mRNA expression was detected by Real-Time PCR assay. Transwell test was applied to detect levels of invasion and migration of the MDA-MB-231 cells. Western blotting was applied to detect expression levels of TG2, MMP-9 and Vimentin. Cancer tissue samples were studied for TG2 expression from 81 patients. RESULTS: RT-PCR assay showed that TGM2 mRNA expression level of RNAi group was 0.21±0.03, and was significantly reduced compared with Con group (1, z=-2.087, P=0.036 9) and NC group(0.94±0.05, z=-1.964, P=0.049 5). The cell numbers of invasion in RNAi group (42.33±4.04) were decreased when compared with Con group (93.50±7.42) and NC group (87.25±5.74) (both z=-2.121, both P=0.0339). The cell numbers of migration in RNAi group (66.13±4.59) were reduced when compared with Con group (116.75±7.82) and NC group (109.00±7.79; both z=-2.309, both P=0.0209). Analysis by Western blotting indicated that TG2 expressions of RNAi group, NC group and Con group were 0.34±0.06, 0.87±0.10 and 0.95±0.03 (F=66.55, P<0.001). The expressions of Vimentin of RNAi group (0.45±0.05) were markedly reduced in contrast to those of NC group (0.89±0.07) and Con group (0.90±0.03, F=80.56, P<0.001). MMP-9 expression levels of RNAi group, NC group and Con group were 0.09±0.02, 0.18±0.03 and 0.19±0.04 (F=12.89, P=0.007). Between the TG2 expressions, we found no significant differences in the distribution according to age, histological grade or menopause. However, we did observe significant correlations of TG2 with lymph node metastasis (χ2=14.75, P<0.001), ER(χ2=11.632, P=0.001) and TNM stage (χ2=13.506, P<0.001). Spearman correlation analysis showed that TG2 was correlated with Vimentin(r=0.337, P=0.002) and MMP-9( r=0.358, P=0.001). CONCLUSION: These observations imply that TG2 may promote invasion and metastasis of breast carcinoma and downregulation of TG2 may be a new therapeutic approach to prevent the development of the metastatic phenotype. ©, 2015, The Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.

He W.,Guangxi Medical University | Sun Z.,Jiangxi Provincial Cancer Hospital | Liu Z.,Guangxi Medical University
Experimental and Therapeutic Medicine | Year: 2015

Epithelial to mesenchymal transition (EMT) plays a critical role in drug resistance. The aim of the present study was to further elucidate its role by examining the effect of tissue transglutaminase (TG2) on EMT and drug resistance in breast cancer. An antisense lentiviral (LV) short hairpin (sh)RNA construct specific to the TG2 gene (TGM2) was designed, synthesized and stably transfected into MDA-MB-231 cells to silence TGM2 by RNA interference (RNAi). The transfected cells expressed low levels of TG2 and constituted the RNAi (TGM2-shRNA) group. A control (NC) group was also established by transfecting MDA-MB-231 cells with scrambled shRNA. The expression levels of TG2, E-cadherin, vimentin and B-cell lymphoma (Bcl)-2 in the cells were examined via western blotting. The transfected MDA-MB-231 cells were divided into four groups, two of which were treated with doxetaxel (TXT): NC, RNAi, TXT and RNAi + TXT groups,. Cell proliferation was analyzed by MTT assay and cell apoptosis was detected by flow cytometry. An in vivo assay was also conducted, in which MDA-MB-231 cells transfected with scrambled shRNA or TGM2-shRNA were subcutaneously implanted into nude mice. After 2 weeks, TXT or vehicle was intraperitoneally administered at a dose of 10 mg/kg on day 1 of every week and tumor growth was monitored. Following the silencing of TGM2 in the MDA-MB-231 cells, the cells showed changes in morphology, indicating that an increased expression of TG2 was associated with a mesenchymal morphology. Transfection of the cells with TGM2-shRNA affected the expression of TG2, E-cadherin, vimentin and Bcl-2. In the MTT assay, the proliferation of MDA-MB-231 cells was significantly inhibited in the RNAi group compared with the control group (P<0.05), and the inhibitory effect increased in a time-dependent manner. Following treatment with TXT for 48 h, apoptosis was significantly promoted in the RNAi + TXT group compared with that in the other groups (P<0.05). Measurement of the tumors in the nude mice indicated that the combination of RNAi and TXT brought about a stronger antitumor effect than either treatment alone. These results suggest that the downregulation of TG2 reversed EMT and modulated the chemosensitivity of breast cancer to TXT. TG2 may be an important predictive and prognostic factor for the treatment efficacy of chemotherapy in patients with breast cancer. © 2015 Spandidos Publications. All rights reserved.

Lu S.,Nanchang University | Lu S.,Jiangxi Province Key Laboratory of Molecular Medicine | Zhou W.,Jiangxi Provincial Cancer Hospital | Wei H.,Jiangxi Provincial Cancer Hospital | And 2 more authors.
Digestive Diseases and Sciences | Year: 2015

Background: Emerging evidence suggests that MTBP plays a role in cancer development and possibly progression, but its influence on hepatocellular carcinoma (HCC) remains unclear. Methods: We used real-time PCR and Western blotting to investigate MTBP expression in four HCC cell lines, 120 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine MTBP expression in HCC and corresponding paracarcinomatous tissues from 120 patients. E-cadherin was only examined in HCC tissues of patients mentioned above. Statistical analyses were applied to evaluate the prognostic value and associations of MTBP expression with clinical parameters. Furthermore, the MTBP gene was overexpressed in HepG2 cell and silenced by siRNA in Hu7 cell, and cell migration and invasion were detected in vitro and in vivo. Moreover, the molecular mechanism of E-cadherin regulation by MTBP was explored. Results: In this study, we first showed that MTBP protein expression is positively correlated with distant metastasis and poor prognosis in HCC patients. We also found that MTBP expression was increased in metastatic cell lines when compared with nonmetastatic cell lines. Consistent with these findings, enhanced expression of MTBP promoted HCC cell invasiveness and metastasis both in vitro and in vivo, whereas the knockdown of MTBP with small interfering RNA resulted in reduced HCC migration and invasion. Ectopic expression of MTBP in HCC cells induced epithelial-to-mesenchymal transition, whereas the silencing of MTBP had the opposite effect. Furthermore, our results show that MTBP and E-cadherin protein expression are inversely correlated in primary HCC tissues. Moreover, our findings indicate that MTBP overexpression decreases E-cadherin expression through the modulation of Mdm2 ubiquitination degradation. Conclusions: Our data show that MTBP aggravates the invasion and metastasis of HCC by promoting the MDM2-mediated degradation of E-cadherin. © 2015, Springer Science+Business Media New York.

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