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We previously found that the relative abundance of Bifidobacterium was increased after chemotherapy; however, the role of Bifidobacterium longum in chemotherapeutic drug resistance in ovarian cancer (OVC) remains unclear. This study aimed to understand the potential effects and mechanism of B. longum extracellular vesicles (B. longum‐EVs) on carboplatin (CBP) resistance in OVC. Eight normal and 11 ovarian tissues were collected and the expression of B. longum genomic DNA and its association with acquired CBP resistance in OVC patients was determined. After isolating EVs by ultracentrifugation from B. longum (ATCC 15707), CBP‐resistant A2780 cells were treated with PBS, CBP, B. longum‐EVs, or CBP + B. longum‐EVs, and subsequently analyzed by CCK‐8, Edu staining, Annexin V/PI double staining, wound healing, and Transwell assays to detect cell viability, proliferation, apoptosis, migration, and invasion, respectively. MRP1, ATP7A, ATP7B, and p53 expression as well as p53 phosphorylation were measured by western blot analysis. S15A mutation of p53 was assessed to examine the potential role of p53 Ser15 phosphorylation in CBP‐resistant OVC. B. longum levels were elevated and positively associated with CBP resistance in OVC patients. Only high concentrations of B. longum‐EVs attenuated A2780 cell proliferation, apoptosis, migration, and invasion. B. longum‐EVs exposure significantly enhanced the sensitivity of CBP‐resistant A2780 cells to CBP and decreased the expression of drug resistance‐related proteins. The effect of B. longum‐EVs on reversing CBP resistance was completely inhibited by S15A mutation of p53. B. longum‐EVs enhanced the sensitivity of OVC cells to CBP through p53 phosphorylation on Ser15. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 and kinase MEKK5 both play an essential role in lung cancer migration. A report predicts that MEKK5 may be ubiquitinated by NEDD4; however, interaction of MEKK5 with NEDD4 and ubiquitination of MEKK5 by NEDD4 have not been characterized. In this report, we show that NEDD4 interacts with MEKK5 through a conserved WW3 domain by the co-immunoprecipitation and the GST-pulldown assays. The ubiquitination assay indicates that MEKK5 is not a ubiquitination substrate of NEDD4, but negatively regulates NEDD4-mediated ubiquitination. Furthermore, overexpression of MEKK5 significantly reduced the NEDD4-promoted lung cancer cell migration. Taken together, our studies have defined an inhibitory role of MEKK5 in regulation of NEDD4-mediated ubiquitination. [ABSTRACT FROM AUTHOR]

Autophagy serves an important role in cancer cell survival and drug resistance. In the present study, the prostate cancer DU145 cell line was used, which lacks autophagy related 5 (ATG5) expression and is defective in induction of ATG5-dependent autophagy. The aim of the study was to examine the effects of the restoration of autophagy on cell proliferation and migration, and to assess the cytotoxicity caused by chemotherapeutic drugs, using microscopic, wound-healing, western blot and apoptotic assays. The restoration of the autophagic activity in DU145 cells by the overexpression of ATG5 enhanced the cell proliferation and migration rates. Notably, restoration of the ATG5-dependent autophagy in DU145 cells significantly increased the cytotoxic effects of the chemotherapeutic drugs, docetaxel and valproic acid, and the endoplasmic reticulum stress inducers, brefeldin A, tunicamycin and thapsigargin. The present study provides a novel perspective on the role of ATG5-dependent autophagy in drug resistance and chemotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] Nicotine, a major alkaloid found in tobacco, is a significant risk factor for gastric cancer. IL-8, a pleiotropic cytokine, plays a vital role in cancer cell metastasis. The role of nicotine in IL-8 expression and the underlying mechanism is currently unknown. Here, we examined the effects of nicotine on IL-8 expression and explored the potential mechanisms in gastric cancer cells. We found that nicotine increases IL-8 expression. Specific inhibitor and mutagenesis studies showed that ROS and MAPK (Erk1/2, p38) were involved in this process. Deletion and site-directed mutagenesis studies indicate the involvement of transcription factor NF-κB and AP-1. ROS and ROS/MAPK (Erk1/2, p38) functioned as the upstream signaling molecules in the activation of NF-κB and AP-1, respectively. AGS gastric cancer cells pretreated with nicotine stimulate angiogenesis in the tumor microenvironment, partially abrogated by silencing IL-8 in AGS cells. In this study, we found that nicotine induces IL-8 expression via ROS/NF-κB and ROS/MAPK (Erk1/2, p38)/AP-1 axis in gastric cancer cells, thus stimulating endothelial cell proliferation and angiogenesis in the tumor microenvironment. [ABSTRACT FROM AUTHOR]