Search

The expression of membrane type-1 matrix metalloproteinase (MT1-MMP) in cancer cells is critical for understanding the development, invasion and metastasis of cancers. In this study, we devised an interference-free surface-enhanced Raman scattering (SERS) nanoprobe with high selectivity and specificity for MT1-MMP. The nanoprobe was comprised of silver core-silica shell nanoparticle with a Raman reporter tag (4-mercaptobenzonitrile) embedded in the interface. Moreover, the nitrile group in 4-mercaptobenzonitrile shows a unique characteristic peak in the Raman-silent region (1800â€"2800 cmâˆ'1), which eliminates spectral overlapping or background interference in the Raman fingerprint region (500â€"1800 cmâˆ'1). After surface modification with a targeting peptide, the nanoprobe allowed visualization and evaluation of MT1-MMP in breast cancer cells via SERS spectrometry. This interference-free, peptide-functionalized SERS nanoprobe is supposed to be conducive to early diagnosis and invasive assessment of cancer in clinical settings. [ABSTRACT FROM AUTHOR]

Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial‐mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC‐823 were treated with cisplatin. Down‐regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer. [ABSTRACT FROM AUTHOR]

Complexation of cisplatin with a p53 activator as a single anticancer agent resulted in synergistically improved cytotoxicity in p53 wild-type but not p53 null human cancer cells. Mechanistic investigation was carried out on this dual-targeting Pt(iv) prodrug, chalcoplatin. The prodrug effectively entered cancer cells and arrested the cell cycle at the S and G2/M phases, distinctive of that from cisplatin. Chalcoplatin significantly induced p53 activation as well as the subsequent apoptosis pathways. This unique mode of action renders chalcoplatin remarkably cytotoxic and makes this compound among the first examples of a Pt(iv) prodrug that directly interacts with the downstream pathway after the formation of Pt–DNA lesions. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have implied that miRNAs act as crucial modulators for epithelial-to-mesenchymal transition (EMT). We found that miR-134 expression correlated with invasive potential and EMT phenotype of NSCLC cells. Functional assays demonstrated that miR-134 inhibited EMT in NSCLC cells. In addition, we showed that Forkhead Box M1 (FOXM1) is a direct target of miR-134. Knockdown of FOXM1 reversed EMT resembling that of miR-134 overexpression. We further found that FOXM1 was involved in TGF-β1-induced EMT in A549 cells. These findings suggest that miR-134 acts as a novel EMT suppressor in NSCLC cells. [Copyright &y& Elsevier]

Abstract: Objective: To investigate whether the serum miR-221 expression correlates with clinicopathologic features and the prognosis of hepatocellular carcinoma (HCC) patients. Methods: Four miRNAs (miR-221, miR-222, miR-21 and miR-224) related to HCC were selected in the present study. Serum miRNA expression was investigated in 46 HCC patients and 20 healthy normal controls by using real-time PCR technique, and then correlations between miR-221 expression and the clinicopathological features and prognosis of HCC patients were evaluated. Results: The four miRNAs were found to be differentially overexpressed in HCC serum samples, and high level of miR-221 expression was correlated with tumor size (P <0.001), cirrhosis (P =0.003) and tumor stage (P =0.016). In addition, Kaplan–Meier survival analysis showed that the overall survival rate of the high miR-221 expression group (27.6%) was significantly lower than that of the low miR-221 expression group (62.3%, P <0.05). Conclusions: Serum miR-221, upregulated in HCC, can provide predictive significance for prognosis of HCC patients. [Copyright &y& Elsevier]

Given the poor prognosis of unresectable advanced gastric cancer (GC), novel therapeutic strategies are needed. The mitogen-activated protein kinase (MAPK) signaling cascade, the most frequently activated pathway in GC, plays an important role in tumorigenesis and metastasis. The MAPK/extracellular signal-regulated kinase (ERK) pathway is an attractive therapeutic target for GC. In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC. • PB suppresses the proliferation and induces the apoptosis of GC cells. • PB inhibits the transcriptional and post-transcriptional activity of STAT3. • PB and trametinib synergistically induce the apoptosis of GC cells. • The combination of PB and trametinib suppresses both ERK and STAT3 phosphorylation. [ABSTRACT FROM AUTHOR]