Schiegnitz Eik, Kämmerer Peer W, Rode Katharina, Schorn Thomas, Brieger Jürgen, Al-Nawas Bilal
Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre, Rostock, Germany.
J Oral Pathol Med. 2016 Jan;45(1):63-9. doi: 10.1111/jop.12323. Epub 2015 Apr 16.
Growth differentiation factor 15 (GDF15) is involved in tumor pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was an investigation of the potential influence of GDF15 on radioresistance of OSCC cells in vitro.
Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF15 expression in the supernatant per survived cell colony was examined with ELISA. Non-irradiated and OSCC cell lines irradiated with 6 Gy were evaluated for GDF15 expression using immunofluorescent staining. For further investigation of GDF15 effects on radioresistance, a GDF15 knockdown model in a human OSCC cell line was established, and apoptotic activity after radiation was measured using the Caspase-Glo 3/7 system.
ELISA and immunofluorescent staining indicated an increased GDF15 expression in 5 OSCC cell lines compared with human gingival epithelial cells. Irradiation with two and six gray resulted in a significant elevation of GDF15 expression per survived cell colony in the irradiated OSCC cell lines (P < 0.001). Furthermore, a dose-dependent expression of GDF15 was seen. Immunofluorescent staining confirmed an elevated GDF15 expression in irradiated OSCC cell lines (n = 10; P ≤ 0.001). Apoptotic activity was significantly increased after irradiation in the GDF15 knockdown group compared with control cells (n = 24; P < 0.001).
This study describes for the first time the vital role of GDF15 both in tumorigenesis and in radioresistance of OSCC cells. With its anti-apoptotic effects, GDF15 possibly promotes tumor progression and might protect carcinoma cells against irradiation effects. Consequently, GDF15 may be a promising therapeutic target in oral cancer.
生长分化因子15（GDF15）参与口腔鳞状细胞癌（OSCC）的肿瘤发病机制。本研究旨在探讨GDF15对体外OSCC细胞放射抗性的潜在影响。
用0、2或6 Gy照射口腔鳞状细胞癌细胞系，用酶联免疫吸附测定法检测每个存活细胞集落上清液中GDF15的表达。使用免疫荧光染色评估未照射和用6 Gy照射的OSCC细胞系的GDF15表达。为进一步研究GDF15对放射抗性的影响，建立了人OSCC细胞系中的GDF15敲低模型，并使用Caspase-Glo 3/7系统测量辐射后的凋亡活性。
酶联免疫吸附测定法和免疫荧光染色表明，与人类牙龈上皮细胞相比，5种OSCC细胞系中GDF15表达增加。用2 Gy和6 Gy照射导致照射的OSCC细胞系中每个存活细胞集落的GDF15表达显著升高（P < 0.001）。此外，观察到GDF15的剂量依赖性表达。免疫荧光染色证实照射的OSCC细胞系中GDF15表达升高（n = 10；P ≤ 0.001）。与对照细胞相比，GDF15敲低组照射后凋亡活性显著增加（n = 24；P < 0.001）。
本研究首次描述了GDF15在OSCC细胞的肿瘤发生和放射抗性中的重要作用。GDF15具有抗凋亡作用，可能促进肿瘤进展，并可能保护癌细胞免受辐射影响。因此，GDF15可能是口腔癌中有前景的治疗靶点。
