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

Abstract

BackgroundMaspin, 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.MethodsMaspin 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.ResultUpregulate 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.ConclusionMaspin could enhance cisplatin chemosensitivity in T24 and 5637 cell lines. Its expression correlated with prognosis of MIBC patients who received cisplatin based neoadjuvant chemotherapy.

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

“…Additional MTS and apoptosis assays revealed that ectopic maspin overexpressed in T24 (T24-Maspin) cells was more sensitive to cisplatin-induced apoptosis than mock-transfected T24 cells were (Figure 2E,F). These results are consistent with those of other studies reporting that the ectopic overexpression of maspin improved the sensitivity of bladder carcinoma cells to cisplatin [23,24]. Moreover, our study demonstrated that maspin blocked tumor growth in vivo when using xenografts of BALB/cAnN-Foxn1 NU mice (Figure 4).…”

Synthetic tetracycline-controllable shRNA targeting long non-coding RNA HOXD-AS1 inhibits the progression of bladder cancer

“…It has become the fourth most common tumor among men with morbidity almost 4 times than that among women [ 1 ]. Approximately 70 % of patients present non-muscle invasive bladder cancer (NMIBC) and patients with muscle-invasive bladder cancer (MIBC) account for the rest [ 2 , 3 ]. Transurethral resection of bladder tumor (TURBT) and intravesical chemotherapy usually have been chosen to treat NMIBC, while radical cystectomy is used for high-grade muscle-invasive bladder cancer (MIBC).…”

Annexin A2 contributes to cisplatin resistance by activation of JNK-p53 pathway in non-small cell lung cancer cells

“…Several mechanisms that mediate cisplatin resistance have been identified, including decreased import, pronounced activity of efflux pumps, increased detoxification, and increased efficiency of DNA repair systems [ 32 – 35 ]. Since DNA damage and the induction of mitochondrial apoptosis are the most critical mechanisms of cisplatin action, evasion of apoptosis might be a key feature of acquired cisplatin resistance in tumor cells [ 36 ].…”