No abstract

AimsThe role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) of pancreatic cancer (PC) is known, however, its mechanism is unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand its mechanism by identifying Gli1 targets in pancreatic cancer cells.MethodsFirst, we investigated invasion, migration, and EMT in PC cells transfected with lentiviral Gli1 interference vectors or SHH over-expression vectors in vitro and in vivo. Next, we determined the target gene profiles of Gli1 in PC cells using cDNA microarray assays. Finally, the primary regulatory networks downstream of SHH-Gli1 signaling in PC cells were studied through functional analyses of these targets.ResultsOur results indicate there is decreased E-cadherin expression upon increased expression of SHH/Gli1. Migration of PC cells increased significantly in a dose-dependent manner within 24 hours of Gli1 expression (P<0.05). The ratio of liver metastasis and intrasplenic miniature metastasis increased markedly upon activation of SHH-Gli1 signals in nude mice. Using cDNA microarray, we identified 278 upregulated and 59 downregulated genes upon Gli1 expression in AsPC-1 cells. The data indicate that SHH-Gli1 signals promote EMT by mediating a complex signaling network including TGFβ, Ras, Wnt, growth factors, PI3K/AKT, integrins, transmembrane 4 superfamily (TM4SF), and S100A4.ConclusionOur results suggest that targeting the molecular connections established between SHH-Gli1 signaling and EMT could provide effective therapies for PC.

FOLFOX-4 regimen is a feasible and moderately efficacious second-line chemotherapy for advanced BTC.

Background Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. Results Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusions This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

Dickkopf-related protein 4 (DKK4) is a target of the β-catenin/transcription factor 4 complex in colorectal cancer. Previous research has demonstrated that its expression level may vary and has indicated that it may have a role in the development of resistance to chemotherapy in colorectal cancer cells. In the present study, DKK4 was over expressed in several colorectal cancer cell lines. The DKK4 over-expressing cell lines were screened using reverse transcription quantitative polymerase chain reaction analysis and western blotting. Analysis of cell viability in the control and DKK4 over-expressing cell lines, following treatment with 5-fluorouracil (5-Fu), YN968D1 or both, indicated that DKK4 over-expressing cells exhibit increased drug resistance. The results of Transwell chamber assays suggested that DKK4 had an effect on cell migration. Furthermore, the results from flow cytometric analysis showed that the percentage of apoptotic cells was reduced in the DKK4 over-expressing cell lines, following drug treatment, compared with the control. The present data suggested that DKK4 may enhance the resistance of colorectal cancer cells to 5-Fu and YN968D1 treatment, when used alone or in combination.