Tao Huang

Osteosarcoma is the most common primary malignant bone tumor among children and young people and is associated with poor prognosis. Punicalagin is an antioxidant ellagitannin found in pomegranate juice with known antiproliferation and anti‑angiogenesis properties. However, the antitumor effect of punicalagin on osteosarcoma requires further investigation. In the present study, the inhibitory effect of punicalagin on proliferation and invasion was evaluated in one human osteoblast cell line (hFOB1.19) and three human osteosarcoma cell lines (U2OS, MG63 and SaOS2). The cancer cell apoptosis ratio was determined using flow cytometry. NF‑κB signaling in these cells was also evaluated using western blotting analysis. A subcutaneous tumor xenograft model was initiated to study the efficacy of punicalagin on osteosarcoma development and angiogenesis in vivo. Punicalagin treatment significantly decreased osteosarcoma cell proliferation and increased apoptosis. In addition, the invasion potential of these cells in a transwell assay was also dramatically suppressed in osteosarcoma cells. Punicalagin not only induced the degradation of IκBα but also the nuclear translocation of p65, suggesting the attenuation of NF‑κB signaling pathway following treatment. Moreover, punicalagin markedly downregulated interleukin (IL)‑6 and IL‑8 levels, which was consistent with the inhibition of NF‑κB signaling. An NF‑κB activator could reverse these effects. Using a tumor xenograft mouse model, it was demonstrated that punicalagin exposure inhibited osteosarcoma growth and angiogenesis in vivo. These observations confirmed the suppressive effect of punicalagin against osteosarcoma malignancies. The underlying molecular mechanisms may include inhibition of the NF‑κB signaling pathway.

Lung cancer is one of the leading malignancies worldwide, but the regulatory mechanism of its growth and metastasis is still poorly understood. We investigated the possible expression of immunoglobulin G (IgG) genes in squamous cell carcinomas and adenocarcinomas of the lung and related cancer cell lines. Abundant mRNA of IgG and essential enzymes for IgG synthesis, recombination activation genes 1, 2 (RAG1, 2) and activation-induced cytidine deaminase (AID) were detected in the cancer cells but not in adjacent normal lung tissue or normal lung epithelial cell line. The extents of IgG expression in 86 lung cancers were found to associate with clinical stage, pathological grade and lymph node metastasis. We found that knockdown of IgG with siRNA resulted in decreases of cellular proliferation, migration and attachment for cultured lung cancer cells. Metastasis-associated gene 1 (MTA1) appeared to be co-expressed with IgG in lung cancer cells. Statistical analysis showed that the rate of IgG expression was significantly correlated to that of MTA1 and to lymph node metastases. Inhibition of MTA1 gene expression with siRNA also led to decreases of cellular migration and attachment for cultured lung cancer cells. These evidences suggested that inhibition of cancer migration and attachment induced by IgG down-regulation might be achieved through MTA1 regulatory pathway. Our findings suggest that lung cancer-produced IgG is likely to play an important role in cancer growth and metastasis with significant clinical implications.

The engagement of sexual behaviors is regulated by a number of factors which include gene expression, hormone circulation, and multi-sensory information integration. In zebrafish, when a male and a female are placed in the same container, they show mating-like behaviors regardless of whether they are kept together or separated by a net. No mating-like behaviors are observed when same-sex animals are put together. Through the olfacto-visual centrifugal pathway, activation of the terminalis nerve in the olfactory bulb increases GnRH signaling in the brain and triggers mating-like behaviors between males. In zebrafish mutants or wild-type fish in which the olfacto-visual centrifugal pathway is impaired or chemically ablated, in response to odor stimulation the mating-like behaviors between males are no longer evident. Together, the data suggest that the combination of olfactory and visual signals alter male zebrafish's mating-like behaviors via GnRH signaling.