Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, No.270, Dong'An Road, Xuhui District, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Ovarian Res. 2021 Oct 2;14(1):128. doi: 10.1186/s13048-021-00884-z.
Drug resistance and recurrence are main contributors to the poor prognosis of ovarian cancer. Cisplatin is a platinum compound which is widely used in the treatment of various solid tumors including ovarian cancer. Up to now, the mechanism of cisplatin resistance in ovarian cancer is unclear. Threonine and tyrosine kinase (TTK), an integral part of the spindle assembly checkpoint, may be a potential new target associated with chemotherapy sensitivity.
TTK was up-regulated in the cisplatin-resistant ovarian cancer cell line. Down-regulation of TTK could recover the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin treatment. Mechanistically, the PI3K/AKT signaling pathway was activated in cisplatin-resistant cells, and this pathway would be affected by TTK expression. Furthermore, TTK was highly expressed in the tissues of ovarian cancer patients, especially those acquired resistance to cisplatin.
Our study revealed that TTK may be a promising therapeutic target for cisplatin-resistant ovarian cancer.
耐药性和复发是导致卵巢癌预后不良的主要原因。顺铂是一种铂类化合物,广泛用于治疗包括卵巢癌在内的各种实体瘤。迄今为止,卵巢癌顺铂耐药的机制尚不清楚。丝氨酸/苏氨酸激酶(TTK)是纺锤体组装检查点的一个组成部分,可能是与化疗敏感性相关的一个潜在的新靶点。
TTK 在顺铂耐药卵巢癌细胞系中上调。下调 TTK 可以恢复顺铂耐药卵巢癌细胞对顺铂治疗的敏感性。在机制上,PI3K/AKT 信号通路在顺铂耐药细胞中被激活,而该通路受 TTK 表达的影响。此外,TTK 在卵巢癌患者的组织中高度表达,特别是那些对顺铂耐药的患者。
我们的研究表明,TTK 可能是治疗顺铂耐药卵巢癌的有前途的靶点。