Prx1 Knockdown Inhibits Nicotine-induced OSCC Lymphatic Metastasis in Mice

Objectives: Oral cancer is more common malignant neoplasm, tobacco is a major risk factor for the pathogenesis of oral cancer. Peroxiredoxin 1 (Prx1) was reported to be related to tumor growth and metastasis, however, the role and molecular mechanism is not fully understood.
Methods: The cell migration and invasion were detected by In vitro scratch assay and Matrigel invasion assay in CAL 27 cells treated with nicotine. The expression of Peroxiredoxin1 (Prx1), E26 transformation specific1 (Ets-1), epithelial-to-mesenchymal transition (EMT) marker E-cadherin, vimentin and Snail were investigated by qRT-PCR and Western blot. And we established a mouse model for the cervical lymph node metastasis in tongue cancer to confirm the roles of nicotine in OSCC in vivo.
Results: In this study, we showed that nicotine enhanced cell invasion and migration, upregulated the expression of Prx1,Ets-1 and vimentin, downregulated the expression of E-cadherin in CAL 27 cells. After Prx1 knockdown, the invasion and migration were inhibited, the expression of E-cadherin was upregulated, the expression of vimentin and Snail was downregualted in CAL 27 cells. In addition, we developed cervical lymphatic metastasis model using orthotopic transplantation of Prx1 knockdown CAL 27 cells labeled with GFP into the tongues of nude mice. We found that nicotine induced cervical lymphatic metastases of OSCC cells in mouse tongues. Prx1 knockdown inhibited mouse cervical lymphatic metastasis, upregulated E-cadherin expression and downregulated the expression of vimentin and Snail in the tongue and lymph node tussues.
Conclusions: The results indicate that nicotine promotes OSCC lymphatic metastasis via the regulating Prx1/EMT signalling in the pathogenesis of OSCC. Prx1 may represent a potential target for the prevention and treatment of OSCC.