Department of Oral Pathology and Medicine, Dental School, National and Kapodistrian University of Athens, 2 Thivon Str. Goudi, 11527, Athens, Greece.
Pathol Oncol Res. 2020 Jan;26(1):183-192. doi: 10.1007/s12253-018-0405-9. Epub 2018 Mar 21.
p38 protein belongs to Mitogen-activated protein kinases family that link extracellular stimuli with intracellular responses participating in numerous of fundamental cell processes. Persistent activation of STAT3 has been associated with cell proliferation, differentiation and apoptosis in oral squamous cell carcinoma (OSCC). This study examines the effects of p38 modulation on STAT3 signaling and cellular activities in OSCC cells and investigates possible correlation of p38 expression with tumor degree of differentiation. Phospho-p38 immunostaining was performed in 60 OSCC including well, moderately and poorly differentiated tumors. Semiquantitative analysis was used, by calculating intensity, percentage and combined scores. Protein expression levels of STAT3 (total, tyrosine and serine phosphorylated), p38 and cyclin D1 were assessed in two OSCC cell lines. p38 inhibition was achieved by pharmacological agent(SB2023580). Cell proliferation and viability rates were also evaluated. Phospho-p38 immunoexpression was intense in almost all tumor specimens, nevertheless did not correlate with tumor differentiation. Inhibition of p38 with SB203580 did not appear to affect tyrosine or serine phosphorylated STAT3 as well as cyclin D1 levels in both cell lines. Moreover, p38 inhibition resulted in mild dose-dependent decreases in cell growth and viability in both cell lines. p38 is highly expressed in OSCC but does not seem to mediate the oncogenic STAT3 pathway. However, changes found in proliferation and viability may suggest that p38 functions as potent regulator of HNSCC. Understanding the complexity of p38 signaling and cross-talk between other major molecules, may guide the development of novel pharmacologic therapies for cancer treatment and prevention.
p38 蛋白属于丝裂原活化蛋白激酶家族，它将细胞外刺激与参与众多基本细胞过程的细胞内反应联系起来。STAT3 的持续激活与口腔鳞状细胞癌（OSCC）中的细胞增殖、分化和凋亡有关。本研究研究了 p38 调节对 OSCC 细胞中 STAT3 信号和细胞活性的影响，并研究了 p38 表达与肿瘤分化程度的可能相关性。在 60 例 OSCC 中进行了磷酸化 p38 免疫染色，包括分化良好、中度和低度分化的肿瘤。通过计算强度、百分比和综合评分进行半定量分析。在两种 OSCC 细胞系中评估了 STAT3（总、酪氨酸和丝氨酸磷酸化）、p38 和细胞周期蛋白 D1 的蛋白表达水平。使用药理试剂（SB2023580）抑制 p38。还评估了细胞增殖和活力率。磷酸化 p38 在几乎所有肿瘤标本中均呈强阳性，但与肿瘤分化无关。用 SB203580 抑制 p38 似乎不会影响两种细胞系中酪氨酸或丝氨酸磷酸化 STAT3 以及细胞周期蛋白 D1 的水平。此外，p38 抑制导致两种细胞系的细胞生长和活力呈轻度剂量依赖性降低。p38 在 OSCC 中高度表达，但似乎不会介导致癌 STAT3 途径。然而，在增殖和活力方面发现的变化可能表明 p38 作为 HNSCC 的有效调节剂发挥作用。了解 p38 信号转导的复杂性和其他主要分子之间的串扰，可能为癌症治疗和预防的新型药物治疗提供指导。
