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Published on: June 7, 2019
Targeted Knockdown of Macrophage Migration Inhibitory Factor Enhances UVB Irradiation-Induced Apoptosis Via
Tian Chen1, Qibing Chen2, Fen Li3
1Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
Abstract:
Objectives: We investigated the effects of macrophage migration inhibitory factor (MIF) knockdown or overexpression combined with ultraviolet radiation B (UVB) irradiation on cell proliferation and apoptosis of oral squamous cell carcinoma (OSCC). Methods: MIF expression in OSCC and adjacent tissues was detected by immunohistochemistry. MIF expression in human immortalized oral epithelial cells (HIOEC) and OSCC cells was detected by western blotting. MIF was knocked down or overexpressed in OSCC cell lines (SCC-25 and CAL-27). OSCC cells were set up into control (CON), MIF overexpression/knockdown (oeMIF/shMIF), CON + UVB, and oeMIF + UVB/shMIF + UVB groups based on their exposure to UVB irradiation. Cell line proliferation was studied using a cell counting kit-8 (CCK-8) and colony formation assays. Flow cytometry was applied for determination of apoptosis, cell cycle, reactive oxygen species (ROS) abundance, and mitochondrial membrane potential. Apoptosis-related proteins were assayed by western blotting. Results: The expression of MIF was significantly higher in OSCC tissues and cell lines than in adjacent tissues and HIOEC. MIF knockdown accompanied by UVB irradiation significantly hampered cell viability and proliferation compared to MIF knockdown or UVB irradiation alone. Western blotting and flow cytometry showed that MIF knockdown combined with UVB irradiation not only induced apoptosis via the mitochondrial pathway but also mediated the cell cycle. Flow cytometry showed that ROS and mitochondrial membrane potential depolarization were increased in the combination treatment groups compared with the mono-treatment groups. Additionally, the ROS scavenger N-acetylcysteine significantly attenuated MIF knockdown combined with UVB irradiation-induced apoptosis and reversed MIF knockdown combined with UVB irradiation-induced MAPK activation. Conclusion: MIF knockdown combined with UVB irradiation significantly inhibited the proliferation of OSCC cells. MIF was involved in UVB-induced ROS generation and enhanced UVB irradiation-induced mitochondria-dependent apoptosis of OSCC cells by activating the MAPK pathway. This suggests that MIF-targeted therapy combined with UVB irradiation may be a novel approach for treating OSCC.
Insights
Macrophage migration inhibitory factor (MIF) knockdown combined with ultraviolet radiation B (UVB) significantly inhibits oral squamous cell carcinoma (OSCC) proliferation by inducing apoptosis. This combination therapy shows promise for OSCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with complex pathogenesis.
- Macrophage migration inhibitory factor (MIF) is implicated in cancer progression and immune evasion.
- Ultraviolet radiation B (UVB) is a known carcinogen and therapeutic agent in some skin cancers.
Purpose of the Study:
- To investigate the synergistic effects of macrophage migration inhibitory factor (MIF) modulation and ultraviolet radiation B (UVB) on OSCC cell behavior.
- To elucidate the underlying molecular mechanisms, including apoptosis, cell cycle, reactive oxygen species (ROS) generation, and mitochondrial function.
Main Methods:
- Immunohistochemistry and western blotting were used to assess MIF expression in OSCC tissues and cell lines.
- OSCC cell lines underwent MIF knockdown or overexpression, followed by exposure to UVB irradiation.
- Cell proliferation (CCK-8, colony formation), apoptosis, cell cycle, ROS levels, and mitochondrial membrane potential were analyzed using flow cytometry and western blotting.
Main Results:
- MIF expression was significantly elevated in OSCC compared to normal tissues.
- Combined MIF knockdown and UVB irradiation markedly reduced OSCC cell viability and proliferation.
- The combination treatment induced mitochondrial-dependent apoptosis, altered cell cycle progression, increased ROS production, and depolarized mitochondrial membrane potential, partly via MAPK pathway activation.
Conclusions:
- MIF knockdown potentiates UVB-induced inhibition of OSCC cell proliferation.
- MIF plays a crucial role in UVB-induced ROS generation and mitochondria-dependent apoptosis in OSCC cells.
- Targeting MIF in conjunction with UVB irradiation presents a potential novel therapeutic strategy for OSCC.
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