Objectives: FOXA2 gene methylation links to the progression of cancers, but has not been documented in oral cancer. Herein, we explore the role of FOXA2 in the migration of oral cancer cells. Material and Methods:Methylation-specific PCR was applied for gene methylation.Wound healing and transwell experiments were tested for cell migration. FOXA2 expression in oral cancer tissues was addressed by immunohistochemistry, followed by statistical analysis of its association with clinical manifestations and patient survival.Results: FOXA2 bound to the promoter of CDH1 and enhanced the expression of its gene product E-cadherin, and decreased the cancer cell migration activity. High FOXA2 expression in oral cancer tissues was associated with high E-cadherin expression, decreased lymph node metastasis, and increased patient survival. Conclusion: FOXA2-E-cadherin link is involved in regulation of oral cancer cell metastasis and provides a new insight for the tumor suppressor activity of FOXA2 in oral cancer. K E Y W O R D S cell migration, E-cadherin, FOXA2, gene methylation, oral cancer | 757 BOW et al.

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Background: Oral cancer is a common cancer with a high mortality rate. While surgery is the most effective treatment for oral cancer, it frequently causes deformity and dysfunction in the orofacial region. In this study, methyl aminolevulinate photodynamic therapy (MAL-PDT) as a prevention tool against progression of precancerous lesion to oral cancer was explored. Methods:For in vitro studies, we evaluated the effects of MAL-PDT on viability of DOK oral precancerous cells by XTT, cell morphology by TEM, and intracellular signaling pathways by flow cytometry, Western blotting, and immunofluorescence. For in vivo study, DMBA was used to induce oral precancerous lesions in hamsters followed by MAL-PDT treatment. We measured tumor size and body weight weekly. After sacrifice, buccal pouch lesions were processed for H&E stain and immunohistochemistry analysis. Results: MAL-PDT induced autophagic cell death in DOK oral precancerous cells. The autophagy-related markers LC3II and p62/SQSTM1 and autophagosome formation in DOK cells were increased after MAL-PDT treatment. In vivo, Metvix ® -PDT treatment decreased tumor growth and enhanced LC3II expression in hamster buccal pouch tumors induced by DMBA.

Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib. The cell death was investigated by propidium iodide staining and apoptosis-related proteins were detected by western blotting. Olaparib suppressed cisplatin-induced cell death in K562 and MEG01 cells. Moreover, PARP-1 knockdown also attenuated cisplatin toxicity in CML cells. Inhibition of PARP decreased cisplatin toxicity by attenuating caspase-3 and caspase-9 activity. These results indicated that the toxicity of cisplatin in CML cells requires PARP activity. Therefore, PARP inhibitors may not be useful with DNA-damaging agents such as cisplatin in CML treatment.