Stathmin guides personalized therapy in oral squamous cell carcinoma
Stathmin guides personalized therapy in oral squamous cell carcinoma
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Stathmin 指导口腔鳞状细胞癌的个体化治疗
DOI：
10.1111/cas.14323
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发表时间：
2020-02-17
期刊：
影响因子：
5.7
通讯作者：
Zhong, Lai-ping
中科院分区：
文献类型：
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作者：
Ju, Wu-tong;Ma, Hai-long;Zhong, Lai-ping
多西紫杉醇、顺铂和5-氟尿嘧啶（TPF）诱导化疗在口腔鳞状细胞癌（OSCC）患者中的生存获益并不令人满意。在此之前，我们发现一种微管不稳定蛋白stathmin在OSCC中过度表达。在这里，我们进一步研究了它作为影响OSCC化学敏感性的生物标志物的作用。我们分析了安定素对TPF诱导化疗的预测价值及其对OSCC细胞化疗敏感性的影响。然后，我们进一步研究了TPF化疗联合PI3K-AKT-mTOR抑制剂在体外和体内的治疗效果。我们发现stathmin低表达的OSCC患者受益于TPF诱导化疗，而stathmin高表达的OSCC患者不能受益于TPF诱导化疗。statthmin过表达促进细胞增殖，降低OSCC细胞对TPF的敏感性。此外，抑制PI3K-AKT-mTOR信号通路可降低镇静素的表达和磷酸化。TPF化疗和PI3K-AKT-mTOR抑制剂联合治疗在体外和体内均显示出强大的抗肿瘤作用。因此，安定素可以作为TPF诱导化疗的预测性生物标志物，基于安定素表达的联合治疗方案可能提高OSCC患者的生存率。
The survival benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy in oral squamous cell carcinoma (OSCC) patients is not satisfactory. Previously, we identified that stathmin, a microtubule-destabilizing protein, is overexpressed in OSCC. Here, we further investigated its role as a biomarker that impacts on OSCC chemosensitivity. We analyzed the predictive value of stathmin on TPF induction chemotherapy and its impact on OSCC cell chemosensitivity. Then, we further investigated the therapeutic effects of the combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors in vitro and in vivo. We found that OSCC patients with low stathmin expression benefited from TPF induction chemotherapy, while OSCC patients with high stathmin expression could not benefit from TPF induction chemotherapy. Stathmin overexpression promoted cellular proliferation and decreased OSCC cell sensitivity to TPF treatment. In addition, inhibition of the PI3K-AKT-mTOR signaling pathway decreased stathmin expression and phosphorylation. The combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors exhibited a potent antitumor effect both in vitro and in vivo. Therefore, stathmin can be used as a predictive biomarker for TPF induction chemotherapy and a combination therapy regimen based on stathmin expression might improve the survival of OSCC patients.