Maspin enhances cisplatin chemosensitivity in bladder cancer T24 and 5637 cells and correlates with prognosis of muscle-invasive bladder cancer patients receiving cisplatin based neoadjuvant chemotherapy.
Maspin enhances cisplatin chemosensitivity in bladder cancer T24 and 5637 cells and correlates with prognosis of muscle-invasive bladder cancer patients receiving cisplatin based neoadjuvant chemotherapy.
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Maspin 增强膀胱癌 T24 和 5637 细胞的顺铂化疗敏感性，并与接受基于顺铂的新辅助化疗的肌层浸润性膀胱癌患者的预后相关。
DOI：
10.1186/s13046-015-0282-y
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发表时间：
2016-01-06
期刊：
影响因子：
--
通讯作者：
Zu X
中科院分区：
文献类型：
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作者：
Chen J;Wang L;Tang Y;Gong G;Liu L;Chen M;Chen Z;Cui Y;Li C;Cheng X;Qi L;Zu X
Maspin是丝氨酸蛋白酶抑制剂超家族的非抑制性成员，在多种癌症类型中被表征为肿瘤抑制基因。化疗药物不敏感是有效治疗肌层浸润性膀胱癌（MIBC）的主要障碍之一。本研究旨在探讨Maspin在体外对膀胱癌和MIBC患者顺铂化疗增敏的作用及其可能机制。在两种MIBC细胞系（T24和5637）中通过qRT-PCR定量Maspin表达。通过脂质体转染法成功建立Maspin过表达模型后，采用MTT法和细胞凋亡实验检测MIBC对顺铂的敏感性。Western blot检测PI 3 K/ AKT/mTOR信号通路及凋亡相关分子Caspase 3和Bcl-2的表达。此外，我们评估了Maspin表达和预后的62例MIBC谁接受顺铂为基础的新辅助化疗（NACT）使用免疫组化。上调Maspin表达可增强顺铂对T24和5637细胞的化疗敏感性。转染Maspin后，细胞存活率、克隆形成能力和IC 50降低，凋亡率升高。在Maspin组中，磷酸化（p）-AKT、PI 3 K、mTOR和Bcl-2表达显著降低，而Caspase 3显著增加。在临床研究中，Maspin表达与接受顺铂为基础的NACT的MIBC患者的总生存期（OS）和无进展生存期（PFS）率显著相关。Maspin可增强T24和5637细胞对顺铂的化疗敏感性。其表达与接受顺铂为基础的新辅助化疗的MIBC患者的预后相关。
Maspin, a non-inhibitory member of the serine protease inhibitor superfamily, has been characterized as a tumor suppressor gene in multiple cancer types. Chemotherapeutic insensitivity is one of major obstacles to effectively treating muscle invasive bladder cancer (MIBC). This study was conducted to investigate the role and probable mechanism of Maspin enhancing cisplatin chemosensitivity of bladder cancer in vitro and MIBC patients. Maspin expression was quantified by qRT-PCR in two MIBC cell lines (T24 and 5637). After successful established Maspin overexpression model by lipidosome transfection, MTT and cell apoptosis assay were used to assess the MIBC’s cisplatin sensitivity. Western blot method was used to test PI3K/ AKT/mTOR signal passway and apoptosis related molecules Caspase3 and Bcl-2. Additionally, we evaluated Maspin expression and prognosis in 62 MIBC cases who underwent cisplatin based neoadjuvant chemotherapy (NACT) using immunohistochemistry. Upregulate Maspin expression could enhance the chemosensitivity induced by cisplatin in T24 and 5637 cell lines. The cell viability, cloning ability and IC50 were reduced while apoptosis rate was upregulated when cells were transfected Maspin. Phospho(p)-AKT, PI3K, mTOR, and Bcl-2 expression were significantly decreased, whereas Caspase3 was greatly increased in the Maspin group. In the clinic study, there was significant correlation between Maspin expression and overall survival (OS) and progression-free survival (PFS) rate in MIBC patients who received cisplatin based NACT. Maspin could enhance cisplatin chemosensitivity in T24 and 5637 cell lines. Its expression correlated with prognosis of MIBC patients who received cisplatin based neoadjuvant chemotherapy.