Study for therapeutic strategy using the target protein expressionsystem based on protein stabilization/destabilization in the cancertracing mechanism

我们研究外源因素刺激下口腔鳞癌（OSCC）细胞中基因/蛋白表达的调控以及OSCC细胞的耐药情况，以期在肿瘤示踪机制中建立基于蛋白稳定/不稳定的靶蛋白表达系统，从而制定抗癌治疗策略。IL-22治疗后，OSCC细胞下调角质形成细胞分化相关基因，上调SERPINB3/4 （SCCA1/2）的表达。这些结果表明，IL-22和IL-6激活stat信号通路的差异取决于OSCC的类型。当对V-ATPase抑制剂有抗性的OSCC细胞与SAHA联合处理时，这些细胞STAT信号通路发生改变，对V-ATPase抑制剂更加敏感。总之，这些发现表明V-ATPase可能是一个有吸引力的针对oscc的靶标。此外，V-ATPase抑制剂与SAHA等其他试剂联合可通过改变stat信号通路，诱导V-ATPase抑制剂耐药的OSCC细胞凋亡。综上所述，stat信号通路的调控可能是肿瘤特异性表达系统发展的关键靶点。这些数据的积累可能会导致对这种疾病的新观点的发展，以及潜在的副作用少的新疗法，从而改善OSCC患者的治疗

We studied regulations of gene/protein expression in oral squamous cell carcinoma (OSCC) cells stimulated by exogenous factors and drug-resistance of the OSCC cells in order to develop the anti-cancer therapeutic strategy using the target protein expression system based on protein stabilization/destabilization in the cancer tracing mechanism. The OSCC cells downregulated the keratinocyte differentiation-related genes and upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 and IL-6 differentially activate the STAT-signalingpathway depending on the type of OSCC. When the OSCC cells with resistance to the V-ATPase inhibitor were treated with combination with SAHA, these cells indicated the change in STAT signaling pathway and became more susceptible to the V-ATPase inhibitor. Together these findings suggest V-ATPase could be an attractive target against OSCCs. In addition, combination with other reagents such as SAHA could help V-ATPase inhibitors to induce apoptosis in the V-ATPase inhibitor-resistant OSCC cells via change in STAT-signal pathway. Together, the regulation of STAT-signaling pathway may be a pivotal target for development of the tumor specific expression system. The accumulation of these data could lead to the development of new perspectives on this disease, and potentially new therapies with few side effects, thereby improving the treatment of patients with OSCC