FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway

by Selleckchem | Jun 20 2023

Background: Nasopharyngeal carcinoma (NPC) is the most common head and neck tumor in China. Forkhead box (FOX) proteins have 19 subfamilies, which can maintain cell metabolism, regulate cell cycle and cell growth, etc. FOXK1 is a member of the FOX family, and studies have found that FOXK1 is closely related to tumors.

Objective: This experiment aims to study the effects of FOXK1 interference on proliferation, apoptosis, invasion, epithelial-mesenchymal transition (EMT), and radiosensitivity, by regulating the Janus kinas/signal translator and activator of the transfer 3 (JAK/STAT3) pathway.

Methods: The expression of FOXK1 was detected via immunohistochemistry using clinical nasopharyngeal carcinoma tissues and adjacent tissues. The relationship between FOXK1 expression and tumor stage was subsequently evaluated. The colony formation rate was calculated through the colony formation experiment. Cell apoptosis and cell cycle distribution were detected using flow cytometry, while cell invasion was detected using the Transwell method. The number of cells in the nucleus of each group after 30 min, 4 h, and 24 h of radiotherapy with the 2 Gy dose was counted using immunofluorescence under γ-H2AX focal points of a laser confocal microscope.

Results: FOXK1 is clearly expressed in the patients' cancer tissues. The expression of FOXK1 was significantly correlated with the patient's sex. FOXK1 interference or Peficitinib can upregulate the apoptosis rate of 5-8 F and CNE-2 cells; increase the G2 phase of cells; and inhibit the invasion, migration, and EMT of cells. At the same time, FOXK1 interference can downregulate the protein expression of p-JAK1, p-JAK2, and p-STAT3 in cells. Interference from FOXK1 or Peficitinib alone can reduce the rate of cell colony formation under different radiation doses, and enhance the green fluorescence intensity of γ-H2AX in the nucleus after 4 and 24 h of the 2 Gy dose of radiotherapy. These results are optimal when FOXK1 interference and Peficitinib are used together.

Conclusion: FOXK1 interference in NPC cells can regulate EMT through the JAK/STAT3 signal pathway, enhance the radiosensitivity of cells, and thus inhibit tumor cell progression.

Comments:

The background, objective, methods, and results of the experiment you described can be summarized as follows:

Background: Nasopharyngeal carcinoma (NPC) is the most common head and neck tumor in China. FOX proteins are a family of transcription factors involved in various cellular processes, including cell metabolism, cell cycle regulation, and cell growth. FOXK1 is a member of the FOX family and has been implicated in tumorigenesis.

Objective: The objective of this experiment was to investigate the effects of FOXK1 interference on proliferation, apoptosis, invasion, epithelial-mesenchymal transition (EMT), and radiosensitivity in nasopharyngeal carcinoma cells by modulating the JAK/STAT3 signaling pathway.

Methods: The expression of FOXK1 was examined using immunohistochemistry in clinical nasopharyngeal carcinoma tissues and adjacent tissues. The correlation between FOXK1 expression and tumor stage was evaluated. The colony formation rate was determined by conducting a colony formation assay. Flow cytometry was used to assess cell apoptosis and cell cycle distribution, while cell invasion was measured using the Transwell method. Immunofluorescence under γ-H2AX focal points of a laser confocal microscope was employed to count the number of cells in the nucleus after different durations of radiotherapy with a 2 Gy dose.

Results: FOXK1 expression was detected in the cancer tissues of the patients. The expression of FOXK1 was significantly correlated with the patients' sex. Interfering with FOXK1 or using Peficitinib (a drug) increased the apoptosis rate of 5-8 F and CNE-2 cells, induced cell cycle arrest at the G2 phase, and inhibited cell invasion, migration, and EMT. Moreover, FOXK1 interference downregulated the protein expression of p-JAK1, p-JAK2, and p-STAT3 in cells. Both FOXK1 interference and Peficitinib reduced the rate of cell colony formation under different radiation doses and enhanced the green fluorescence intensity of γ-H2AX in the nucleus after 4 and 24 hours of a 2 Gy dose of radiotherapy. The combined treatment of FOXK1 interference and Peficitinib showed the most favorable results.

Conclusion: Interfering with FOXK1 in NPC cells can modulate EMT through the JAK/STAT3 signaling pathway, enhance cell radiosensitivity, and inhibit tumor cell progression. These findings suggest that FOXK1 may serve as a potential target for therapeutic intervention in nasopharyngeal carcinoma.