Search

Some patients with colon cancer eventually develop metastasis during treatment, and the 5‑year survival rate of patients with metastatic colon cancer remains relatively low, which is most likely due to the ineffectiveness of the current standard treatment. Systemic treatment for patients with colon cancer has expanded from chemotherapy to targeted therapy and immunotherapy. Immunotherapy holds promise in the treatment of colon cancer. The present study revealed the role of innate immune receptor helicase DExD/H‑box helicase 58 (DDX58), which encodes retinoic acid‑inducible gene‑I (RIG‑I), in colon cancer. It was demonstrated that colon cancer patients with a low protein expression of DDX58/RIG‑I had a worse 5‑year survival rate of patients compared with patients with a high expression of DDX58/RIG‑I. The activation of DDX58/RIG‑I inhibited the proliferation, migration and invasion of colon cancer cells, as well as tumor growth in a nude mouse xenograft model of colon cancer. To investigate the mechanisms of action of DDX58/RIG‑I in colon cancer, the role of signal transducer and activator of transcription 3 (STAT3)/cystathionine‑γ‑lyase (CSE) signaling in the up‑ or downregulation of DDX58 was examined. The data demonstrated that DDX58 regulated the STAT3/CSE signaling pathway by interacting with STAT3 and consequently affecting the proliferation of tumor cells in colon cancer. In addition, the RIG‑I agonist, SB9200, induced proliferation, migration and invasion of human colon cancer. On the whole, the present study demonstrates that DDX58/RIG‑I affects the proliferation of tumor cells by regulating STAT3/CSE signaling in colon cancer. The findings presented herein suggest that DDX58/RIG‑I activation may be an effective treatment strategy, and DDX58/RIG‑I agonists may be potential therapeutic candidates for colon cancer.

Background Although epithelial stem/progenitor cells have been isolated from many parts of the human airway epithelium such as lung and trachea, there is limited information in regard to stem cells in nasal epithelium. The aim of this study was to determine if (1) human nasal epithelial stem/progenitor cells (hNESPCs) can be isolated and propagated in vitro and (2) allogeneic adult primary human fibroblasts can serve as a feeder layer for hNESPCs expansion under serum-free conditions. Methods Primary cells taken from inferior turbinate biopsy specimens (n = 3) were enzymically dissociated and plated on either allogeneic human fibroblasts or murine NIH 3T3 fibroblasts, in a chemical-defined medium supplemented with growth factors. Self-renewal, proliferation, and differentiation potential were compared. Results The optimized media were capable of supporting the undifferentiated growth and expansion of hNESPCs on both feeder cells. The doubling time and cloning efficiency of hNESPCs cultured on a human feeder layer were comparable with that cultured on 3T3 feeders. Significantly, the hNESPCs on both feeder layers could be cultured for four passages, and they can differentiate into ciliated columnar cells and goblet cells at the air–liquid interface, resembling the in vivo mucociliary airway epithelium. Conclusion Our results showed the feasibility of expanding hNESPCs for clinical purpose by using human feeder layer, avoiding components of animal source, while preserving their self-renewal and differentiation potential. This study represents an early step toward a better understanding of hNESPCs, and serum -free media plus human feeder potentially would be an ideal method for making clinical grade hNESPCs on a large scale.

Cancer stem cells have been reported as a new therapeutic target in many cancers, but their existence in nasopharyngeal carcinoma (NPC) is largely unknown. This study was conducted to determine cancer stem-like cells in NPC cell line.Basic science experimental study.Aldehyde dehydrogenase (ALDH) activity, a putative functional marker for cancer stem cells, was assessed in Epstein-Barr virus-associated NPC cell line C666-1 cells. The ability of cells with high and low ALDH activity to proliferate, resist therapy, and initiate tumor formation was compared.Enrichment of cancer stem-like cells (with high ALDH activity) in C666-1 was associated with a significantly greater ability to proliferate, be clonogenic, resist chemotherapy drugs and radiation, reconstitute a heterogeneous population, and express pluripotent markers. Furthermore, subcutaneous injection of these cells into immunodeficient nude mice resulted in a tendency of tumor formation at a higher rate as compared to cells with low ALDH activity.These results provide evidence for the existence of cancer stem-like cells in the NPC cell line C666-1 cells.

To investigate the effects of caveolin-1 (CAV1) on the growth of hypopharyngeal squamous cell carcinoma (HSCC) FaDu cells in vitro and in vivo.A CAV1-RNAi-lentivirus construct was transfected into FaDu cells and expression of caveolin-1 was tested by RT-PCR and western blotting analysis. Cell apoptosis was analyzed by transferase-medisated dUTP nick-end labeling (TUNEL) assay. Tumor inhibition effects were investigated by injecting rCAV1-RNAi-lentivirus construct into tumors created with FaDu cells in the HSCC mouse model, with the empty-vector lentivirus as a control. CAV1 expression in xenografts was tested by RT-PCR and immunohistochemistry.RT-PCR and western blot analysis demonstrated successful construction of the CAV1-RNAi-lentivirus construct producing small hairpin RNA. The average weights and volumes of tumor in mice treated with CAV1-RNAi-lentivirus were lower than in mice with control treatment (P0.05). RT-PCR revealed weak positive expression of CAV1 in CAV1-construct-treated xenografts and immunohistochemistry confirmed lower CAV1 expression than in controls.(P0.05). In addition, downregulation of CAV1 increased cell apoptosis in vitro.The growth of HSCCs could be inhibited by recombinant CAV1-RNAi-lentivirus in vitro and in vivo.