Wrenalston5266

PC-3/DTX cells were 10.9-fold resistant to docetaxel in comparison with PC-3 cells. The results showed that PC-3/DTX cells overexpressed Rictor and p-AKT(S473) proteins, which are specific subunits or downstream substrates of mTORC2. The new findings suggested that the mTORC2 signaling pathway may serve an important role in the regulation of docetaxel drug resistance of PC-3 cells. In conclusion, PC-3/DTX cells may be applied to study the resistance of anticancer drugs and to identify methods to overcome resistance.Mesenchymal stem cells (MSCs) exhibit strong tropism towards tumor tissue. While MSCs generally surround tumors, they can also infiltrate tumors and thereby influence their proliferation. Interactions between MSCs and tumor cells are usually tested under normoxia, but the majority of solid tumors, including head and neck squamous cell carcinoma (HNSCC), are also characterized by hypoxic areas. Hence, the present study aimed to assess the interaction between MSCs and tumor cells under hypoxic conditions. MSCs were cultivated under normoxia and hypoxia, and conditioned media were used to cultivate the HNSCC cell line FaDu. The cell cycle distribution and viability of MSCs and the proliferation of FaDu cells were analyzed under normoxia and hypoxia, and changes in cytokine levels in the conditioned media were evaluated. No cell cycle changes were observed for MSCs after 24 h of cultivation under hypoxia, but the cell viability had declined. Hypoxia also led to a decrease in the proliferation of FaDu cells; however, FaDu cells proliferated faster after 48 h under hypoxia compared with normoxic conditions. This effect was reversed after incubation under normoxia for 72 h and hypoxia for 72 h. While these changes constituted a trend, these differences were not statistically significant. A cytokine assay showed an increase in interleukin (IL)-6 in the hypoxic medium. Overall, the results indicated that there was an interaction between MSCs and tumor cells. The presence or absence of oxygen seemed to influence the functionality of MSCs and their protumorigenic properties, in which IL-6 was identified as a potential mediator. Since MSCs are a component of the tumor stroma, further in vitro and in vivo studies are needed to investigate this interaction in order to develop novel approaches for tumor therapy.Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-associated death worldwide. Glioma-associated oncogene homolog 1 (Gli1) is a key component and functions as a reliable marker of Hedgehog signaling pathway activation. Previous studies have demonstrated that Gli1 serves important roles in the progression of various types of cancer, including HCC. However, its effect on HCC invasion and metastasis and the underlying mechanism remain to be elucidated. Small interference RNA was employed to silence the Gli1 gene in liver cancer cells. Reverse transcription-quantitative PCR and western blot analysis were performed to evaluate the mRNA and protein expression of Gli1, respectively. A series of assays, including Cell Counting Kit-8, adhesion, wound healing and Matrigel invasion were performed to investigate cell viability, adhesive, migratory and invasive capabilities of liver cancer cells, respectively. In addition, immunofluorescence staining was performed to determine the cellular localization of focal adhesion kinase (FAK), phosphorylated (p-)FAK and p-AKT. The mRNA and protein expression of Gli1 in liver cancer cells (HepG2 and SK-Hep1) were markedly decreased in a dose-dependent manner following Gli1-knockdown. Gli1 silencing significantly inhibited the adhesion, migration and invasion of SK-Hep1 cells. Additionally, knockdown of Gli1 markedly suppressed the expression of metalloproteinase (MMP)-2 and MMP-9. Furthermore, downregulation of Gli1 blocked the FAK/AKT signaling pathway. Gli1 serves significant roles in the migration and invasion of HCC cells through activation of the FAK/AKT signaling pathway and subsequent upregulation of MMP-2 and MMP-9 expression. Thus, Gli1 may be a potential protein target for the regulation of HCC migration and invasion.Treatment for non-small cell lung cancer (NSCLC) remains challenging due to frequent recurrence and the development of resistance to platinum-based chemotherapy. The mechanism underlying NSCLC chemoresistance remains unclear. The present study aimed to investigate the mechanism of cisplatin resistance in NSCLC cells and it found that the expression of Bcl-2-associated transcription factor 1 (BCLAF1) was higher in the A549 cell line with cisplatin resistance (A549/DDP) by western blotting and reverse-transcription quantitative PCR, suggesting that elevated BCLAF1 expression is associated with acquired cisplatin resistance in A549 cells. BCLAF1 was found to promote DNA damage repair in A549/DDP cells by regulating γH2A histone family member X foci formation by immunofluorescence and western blotting. BCLAF1 was also demonstrated to regulate ubiquitin-specific peptidase 22 mRNA expression in A549/DDP cells, in addition to regulating G1 phase arrest by targeting p21 expression. Taken together, these findings suggest that BCLAF1 mediates cisplatin resistance by regulating the repair of DNA damage and p21-mediated G1 phase arrest.At present, the regulatory mechanisms of various microRNAs (miRNAs/miRs) have been elucidated in human cancers including osteosarcoma (OS). selleck chemicals This study mainly focused on the role of miR-615 in OS, which has not yet been reported. Ninety-two OS tissues and normal samples were used in this study. Human osteoblast hFOB1.19 cells and OS cell line HOS were utilized to detect the expression of miR-615. The expression of miR-615 and gene expression were assessed by RT-qPCR and western blot analysis. Transwell, MTT and luciferase reporter assays were used to investigate the regulatory mechanism of miR-615 in OS. The results revealed that miR-615 expression was reduced in OS tissues and cells, and was associated with poor clinical outcomes and prognosis in OS patients. In addition, overexpression of miR-615 restrained cell viability and metastasis in OS. Furthermore, hexokinase 2 (HK2) was confirmed as a direct target of miR-615. Upregulation of HK2 was detected in OS tissues. The upregulation of HK2 weakened the tumor-suppressive effect of miR-615 in OS.