Pinostilbene Hydrate Inhibits the Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Downregulating MMP-2 Expression and Suppressing Epithelial-Mesenchymal Transition Through the Mitogen-Activated Protein Kinase Signaling Pathways.

Background: Nasopharyngeal carcinoma (NPC) is one of the most common head and neck cancers in East and Southeast Asia. During the past decades, advances in radiotherapy and chemotherapy had shown the improvement in tumor control with fewer side effects. Nevertheless, metastasis of NPC causes treatment failure and is often associated with poor clinical outcome and cancer mortality. Hypothesis/Purpose: Pinostilbene hydrate (PSH) was recently demonstrated to have anti-metastatic properties on human oral cancers. However, the effects of PSH on NPC cells remain unknown. Methods and Results: This study aims to investigate the anti-cancer ability of PSH on human NPC by wound healing, transwell assays, zymography assay, and Western blot assay to explore the possible underlying mechanisms. PSH significantly reduced the migrated distance of NPC cells in a dose-dependent manner and the abilities of cancer cell migration and invasion were markedly inhibited. The activity and the expression of MMP-2 were also significantly decreased after treatment with PSH. Furthermore, combined treatment of PSH with ERK1/2 inhibitor (U0126) caused significant elevation of the activity and the expression of MMP-2. Additionally, PSH upregulated the expression levels of E-cadherin and Claudin-1 while downregulating that of N-cadherin and vimentin on both NPC cell lines. Conclusion: Our research illustrates that PSH inhibits the migration and invasion of human NPC cells. After exposure to PSH on NPC, the expression of MMP-2 is downregulated and EMT is suppressed through MAPK signaling pathways. These observations suggest that PSH could be a potential anti-metastatic agent for patients with NPC.

Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility.

Aberrations of the fibroblast growth factor receptor 4 (FGFR4) genomic region include amplification of FGFR4, activation of FGFR4 kinase domain mutations, and overexpression of FGFR4, which lead to sustained cell proliferation and contribute to tumor development. However, the association between FGFR4 single-nucleotide polymorphisms (SNPs) and risk of oral squamous cell carcinoma (OSCC) remains to be determined. We investigated the relationships between FGFR4 genetic polymorphisms, OSCC development and clinicopathological variables. We recruited a total of 955 patients with OSCC and 1191 controls. Four SNPs of FGFR4 (rs2011077, rs351855, rs7708357, and rs1966265) were examined using real-time polymerase chain reaction. We found that with the rs351855 GA genotype and a combination of the GA and AA genotypes exhibited a 1.431-fold (95% CI: 1.092-1.876) and 1.335-fold (95% CI: 1.033-1.725) higher risk of OSCC. However, patients with OSCC with a homozygous A/A genotype of FGFR4 rs351855 polymorphism had a lower risk of advanced stage OSCC (P = 0.0252). Furthermore, the patients with the FGFR4 rs351855/rs1966265 A-A haplotype had a 2.890-fold (95% confidence interval [CI]: 2.257-3.700) higher risk of OSCC than the controls. Betel quid chewers with the A-A haplotype had a considerably higher risk (95% CI: 16.159-26.937) of OSCC than did betel quid nonchewers with other haplotypes. Moreover, an additional integrated in silico analysis proposed that rs351855 G allele variant to the A allele exhibited a relatively low energy of the transmembrane region. In conclusion, our results suggest that the FGFR4 rs351855 may play a role in susceptibility for OSCC development.

Tanshinone IIA induces apoptosis in human oral cancer KB cells through a mitochondria-dependent pathway.

Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose) polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer.

Progesterone receptor expression in sinonasal leiomyoma: a case report and review of the literature.

Leiomyomas are benign myogenic tumors that seldom occur in the sinonasal cavity. They were commonly found in middle-aged adults with a female predominance. Clinical symptoms include nasal obstruction with discharge, nasal bleeding and pain. We describe the case of a 48 year-old woman with a leiomyoma arising from right inferior nasal turbinate. Transnasal endoscopic excision was performed with satisfied result. The tumor was found to be progesterone receptor positive on immunohistochemical analysis. The clinical findings are addressed with a review of the literature. To the best of our knowledge, this is the third reported case that supports the growth of the tumor may be hormone-dependent.