Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

APE1 shRNA-loaded cancer stem cell-derived extracellular vesicles reverse Erlotinib resistance in non-small cell lung cancer via the IL-6/STAT3 signalling.

OBJECTIVE: Apurinic endonuclease 1 (APE1) has been suggested as an oncogene of lung tumours and our bioinformatics analysis identified the association between Erlotinib resistance and interleukin-6 (IL-6). Thus, we performed this work to delineate the mechanistic actions of APE1/IL-6 signalling in Erlotinib resistance of non-small cell lung cancer (NSCLC). METHODS: We selected human NSCLC cell lines HCC827 and PC9 to establish Erlotinib-resistant HCC827R and PC9R cells. Cancer stem cells (CSCs) were isolated from Erlotinib-sensitive HCC827P and PC9P cells (PCSCs) and from HCC827R and PC9R cells (RCSCs). Further, extracellular vesicles (EVs) were separated from PCSCs (PCSC-EVs) and RCSCs (RCSC-EVs) and co-cultured with RCSCs with or without short hairpin RNA (shRNA)-targeting APE1 (APE1 shRNA) transduction. In addition, functional assays were conducted to determine the effect of APE1 shRNA on malignant phenotypes of cancer cells in vitro and in vivo and the activation of IL-6/STAT3 signalling. RESULTS: It was found that NSCLC cells could internalize both RCSC-EVs and PCSC-EVs. RCSC-EVs augmented the resistance of NSCLC cells to Erlotinib. The overexpression of APE1 occurred in NSCLC tissues, and IL-6 was enriched in serum samples of patients with NSCLC. APE1 shRNA was demonstrated to restrict the Erlotinib resistance of NSCLC cells by inactivating the IL-6/STAT3 signalling. Additionally, shAPE1-loaded RCSC-EVs suppressed the Erlotinib resistance of NSCLC via the IL-6/STAT3 axis both in vitro and in vivo, as reflected by impeded malignant phenotypes and xenograft tumour formation. CONCLUSIONS: Collectively, these data indicate that APE1 confers Erlotinib resistance by activating the IL-6/STAT3 signalling, suggesting targeting APE1 as a possible therapeutic target in Erlotinib-resistant NSCLC.

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling.

SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR, immunohistochemistry, and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan-Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP-induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with low expression of SOX2, and even including its regulating APE1, survived longer than those with high expression of SOX2, and APE1. siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway.

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

Targeting DNAJC19 overcomes tumor growth and lung metastasis in NSCLC by regulating PI3K/AKT signaling.

BACKGROUND: Some driver oncogenes are still unknown in non-small-cell lung cancer (NSCLC). DNAJC19, a major component of the translocation machinery of mitochondrial membranes, is a disease-associated protein. Herein, we report the role of DNAJC19 in NSCLC cell growth and metastasis. METHODS: Immunohistochemistry (IHC) was performed to investigate DNAJC19 expression in NSCLC clinical samples. For knockdown or overexpression assays in A549 or NCI-H1299 lung cancer cells, lentiviral vectors were used. After assessment of cell functions, DNAJC19-knockdown A549 cells were further applied to establish mouse xenograft and metastasis tumor models. Assessments based on the RNA-seq data, western blotting, PCR and IHC were performed for the mechanistic study. RESULTS: Expression of DNAJC19 was higher in tumors than in noncancerous adjacent tissues. Survival analysis indicated that low DNAJC19 levels were correlated with an increased progression-free survival rate. ShRNA-mediated knockdown of DNAJC19 markedly inhibited cell growth, viability, migration and invasion. Moreover, RNA-seq analysis revealed that the PI3K/AKT signaling pathway was involved in molecular events when A549 cells were treated with shDNAJC19. In addition, DNAJC19 knockdown decreased PI3Kp85a, AKT and p-AKT expression in A549 cells, and cellular functions were greatly rescued in DNAJC19-knockdown A549 cells by ectopic overexpression of AKT. Furthermore, tumor xenograft growth and lung metastasis were markedly repressed in the shDNAJC19 group compared to the control group. As expected, the expression levels of DNAJC19, PI3K and AKT in xenograft mouse samples were also lower in the shDNAJC19 group than in the shCtrl group. CONCLUSIONS: DNAJC19 greatly promotes NSCLC cell growth and lung metastasis by regulating PI3K/AKT signaling, providing a novel therapeutic target for treating NSCLC patients.

LigaSure small jaw versus conventional neck dissection: a systematic review and meta-analysis.

BACKGROUND: Neck dissection has a central role in the management of head and neck cancers. This systematic review aimed to compare the intraoperative and postoperative parameters between conventional and LigaSure Small Jaw (LSJ)-assisted neck dissection. METHODS: PubMed (MEDLINE), Embase, and the Cochrane Library were searched. independently by two authors for relevant articles comparing the outcomes of conventional and LSJ-assisted neck dissection. Data from each study were extracted, and a random-effects model was used in the pooled analysis. RESULTS: Compared with conventional techniques, LSJ-assisted neck dissection was associated with a significantly reduced operative time. The rates of postoperative hematoma, infection, amount of intraoperative blood loss, the length of hospital stay and the drainage amount showed no significant intergroup differences. CONCLUSIONS: The meta-analysis provides evidence that properly using LSJ may reduce the operative time compared with that of conventional techniques. Surgeons may consider using LSJ in neck dissection according to personal experiences.

NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-Associated gastric cancer.

Helicobacter pylori infection is an important pathogenic risk factor for gastric cancer, but it is still unclear what tumor markers for gastric cancer induced by H. pylori can be consistently detected. Using an miRNA microarray, we found that miR-18a-3p (6.02-fold) and miR-4286 (5.73-fold) were significantly increased in H. pylori- associated gastric cancer. In a cohort of gastric cancer patients (N = 104), serum expression of miR-18a-3p and miR-4286 was positively and significantly correlated with H. pylori; furthermore, miR-18a-3p was positively correlated with invasion (P = 0.029), and miR-4286 was positively correlated with tumor stage (P = 0.033), tumor size (P = 0.041), and lymph node metastasis (P = 0.009). Overexpression of miR-18a-3p and miR-4286 also increased cancer cell proliferation and motility and both inhibited expression of BZRAP1, resulting in tumor progression in vitro. In addition, lipopolysaccharide co-mediated the expression of miR-18a-3p and miR-4286 by activating the NF-κB transcription factor, but TAK-242 (TLR4 inhibitor) blocked this effect. These results demonstrate that serum miR-18a-3p and miR-4286 levels in H. pylori-associated gastric cancer may be useful prognostic biomarkers and suggest a novel signaling pathway of targeting BZRAP1 in gastric cancer.

Superhydrophilic Coating with Antibacterial and Oil-Repellent Properties via NaIO4-Triggered Polydopamine/Sulfobetaine Methacrylate Polymerization.

Superhydrophilic coatings have been widely used for the surface modification of membranes or biomedical devices owing to their excellent antifouling properties. However, simplifying the modification processes of such materials remains challenging. In this study, we developed a simple and rapid one-step co-deposition process using an oxidant trigger to fabricate superhydrophilic surfaces based on dopamine chemistry with sulfobetaine methacrylate (SBMA). We studied the effect of different oxidants and SBMA concentrations on surface modification in detail using UV-VIS spectrophotometry, dynamic light scattering, atomic force microscopy, X-ray photoelectron spectroscopy, and surface plasmon resonance. We found that NaIO4 could trigger the rate of polymerization and the optimum ratio of dopamine to SBMA is 1:25 by weight. This makes the surface superhydrophilic (water contact angle < 10°) and antifouling. The superhydrophilic coating, when introduced to polyester membranes, showed great potential for oil/water separation. Our study provides a complete description of the simple and fast preparation of superhydrophilic coatings for surface modification based on mussel-inspired chemistry.