The ubiquitin-proteasome system facilitates the degradation of damaged proteins and regulators of growth and stress response. Alterations in this proteolytic system are associated with a variety of human pathologies. By restriction fragment differential display polymerase chain reaction (RFDD-PCR) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF-TOF MS) based on two-dimensional polyacrylamide gel electrophoresis (2-DE), differentially expressed genes and proteins of ubiquitin specific proteases (USPs), proteasome subuinits (PSs) and ubiquitin protein ligase E3A (UBE3A) were analyzed between breast cancer and adjacent normal tissues. Some of them were further verified as over-expression by immunohistochemical stain. Five genes of proteasome subunits (PSs), including PSMB5, PSMD1, PSMD2, PSMD8 and PSMD11, four genes of USPs, including USP9X, USP9Y, USP10 and USP25, and ubiquitin protein ligase E3A (UBE3A) were over-expressed (>3-fold) in breast cancer tissue compared to adjacent normal tissue, and over-expression (>4-fold) of proteins of PSMA1 and SMT3A were observed in breast cancer tissue. PSMD8, PSMD11 and UBE3A were further verified as over-expression by immunohistochemical stain. The action of ubiquitin-proteasome system were obviously enhanced in breast cancer, and selectively intervention in action of ubiquitin-proteasome system may be a useful method of treating human breast cancer.

Our results prove that the oncogenic role of Notch1 in tongue cancer and provide the direction of targeted therapy of tongue cancer.

Background: Numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. The aim of the present study was to identify the role of NOTCH1 in the cell growth and metastasis of SACC.Methods: We analyzed the expression of NOTCH1 in clinical SACC samples using immunohistochemical staining. We silenced the expression of NOTCH1 and overexpressed activated NOTCH1 to elucidate the effects of NOTCH1 on proliferation, migration and invasion. NOTCH1 target genes were validated by real-time PCR.Results: Our results showed that NOTCH1 was upregulated in SACC tissues when compared with normal tissues, and this upregulation was further enhanced in SACC tissues with metastasis and recurrence when compared with SACC tissues without metastasis. Overexpression of NOTCH1 in SACC cells promoted cell growth, migration and invasion, and knockdown of NOTCH1 inhibited cell proliferation in vitro and tumorigenicity in vivo by inducing cell apoptosis.Conclusions:The results of this study suggest that NOTCH1 plays a key role in the cell growth, anti-apoptosis, and metastasis of SACC. NOTCH1 inhibitors might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.

Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), incorporated with online database searching, were performed to investigate differential proteins of breast cancer and adjacent normal breast tissues. Considering that serum albumin is abundantly presented in normal control samples, 15 differential spots detected in 11 out of 12 (91.7%) breast cancer samples were identified by online SIENA-2DPAGE database searching and MALDI-TOF/TOF-MS analysis. The results indicate that pathological changes of breast cancer are concerned with augmentation of substance metabolism, promotion of proteolytic activity, decline of activity of some inhibitors of enzymes, and so on. Some important proteins involved in the pathological process of breast cancer with changed expression may be useful biomarkers, such as alpha-1-antitrypsin, EF-1-beta, cathepsin D, TCTP, SMT3A, RPS12, and PSMA1, among which SMT3A, RPS12, and PSMA1 were first reported for breast cancer in this study.

Lung cancer has a poor 5-year survival rate and is the leading cause of cancer-related deaths worldwide. Thus, the development of more efficient therapeutic strategies is urgently needed. Many studies have shown that EGCG, a major polyphenol found in green tea, has potential anticancer effects. The present study aims to investigate the molecular mechanism of EGCG-mediated inhibition of proliferation in lung cancer cells and to explore the effects of combined treatment with EGCG and an NF-κB inhibitor, BAY11-7082, in A549 and H1299 cells both in vitro and in vivo. Our results showed that EGCG inhibits cell proliferation and migration and induces apoptosis in A549 and H1299 cells at relatively high concentrations (IC50=86.4 µM for A549 cells and 80.6 µM for H1299 cells). These effects are partially achieved via inhibition of the NF-κB signaling pathway. Combined treatment with EGCG and BAY11-7082, a potent NF-κB inhibitor, shows significant synergistic effects at relatively low concentrations. The inhibition rate reached approximately 50% in cells treated for 72 h with 20 µM EGCG and 5 µM (A549 cells) or 2.5 µM BAY11-7082 (H1299 cells). This synergistic anti-tumor effect was also observed in a xenograft model. These results indicated that EGCG inhibits lung cancer cell proliferation by suppressing NF-κB signaling. Coadministration of EGCG and BAY11-7082 has a synergistic effect both in vitro and in vivo and may serve as a novel therapeutic strategy for lung cancer.