Effects of chemotherapy or/and radiotherapy on survivin expression in ovarian cancer

Abstract

Survivin, a member of apoptosis protein inhibitor family, is upregulated in various malignancies, especially in chemotherapy- and/or radiation-resistant cell lines. In this study, the correlation between the level of survivin expression and degree of apoptosis was investigated in three ovarian cancer lines (two chemoresistant cell lines SKOV-3 and OVCAR-3, as well as one chemosensitive cell line OV2008) treated with 5 microg/ml of cisdiamminedichloroplatinum (cisplatin, CDDP) for 24 h, 2 Gy of (60)Co irradiation, or 5 microg/ml CDDP for 3 h plus 2 Gy of (60)Co, respectively. We also evaluated the survivin mRNA abundance in patients with advanced ovarian cancers during CDDP treatment. In the ovarian cancer cell lines, survivin mRNA abundance and protein contents were significantly increased after the treatments while the apoptotic rates did not change in SKOV-3 and OVCAR-3. Moreover, in OVA2008 cells the expression of survivin decreased and the apoptotic rate significantly increased after CDDP and combined treatments. Survivin mRNA was not detectable in normal ovarian tissues and benign ovarian tumors. However, it was observed in the resected tumor specimens from 20 patients with advanced ovarian cancer. These results suggested that survivin may play an important role in the resistance to chemotherapy and radiotherapy in ovarian cancer cell lines and in the progression of ovarian tumors. Survivin may also provide a pivotal prognostic implication for epithelial ovarian carcinomas.

The Association Between the Survivin C-31G Polymorphism and Gastric Cancer Risk in a Chinese Population

“…Importantly, survivin is commonly overexpressed in a wide variety of human malignancies, including gastric cancer [11,12]. Its expression in tumors is implicated in resistance to chemotherapy and radiotherapy [13,14], which was also confirmed in our previous reports [15,16]. Moreover, abundant studies have suggested that survivin is involved in occurrence and development of gastric cancerous invasion and/or metastasis [17][18][19][20].…”

siRNA Directed Against Survivin Enhances Pancreatic Cancer Cell Gemcitabine Chemosensitivity

“…As an anti-apoptotic factor, survivin directly binds to and inhibits both caspase-3 and caspase-7 activity, leading to the arrest of apoptosis. Survivin expression may resist apoptosis induced by chemotherapy agents in tumor cells [34,35]. We suggest that the inhibition of survivin expression could activate caspases and contribute to gemcitabine inducing apoptosis in pancreatic cancer cells.…”

A Novel CRAd in Combination With Cisplatin Enhanced the Antitumor Efficacy in Ovarian Cancer

“…27 The survivin promoter was a cisplatin or radiation-responsive promoter in ovarian cancer cells. 13,14 Cisplatin, a first-line cytotoxic agent, has been studied as an agent of single or combination regimen for ovarian cancer. Nonetheless, 50% to 70% of responders would relapse within approximately 18 months after the completion of the first-line therapy and would The ratio 3:2 or 3:1 is used to illustrate the potential additive or synergistic effects when CRAd-S.GRD was given in combination with cisplatin.…”

“…The survivin promoter activity was reinforced with the treatment of cisplatin in cell lines of gli-oma and ovarian cancer as well as in primary tumor cells. 13 The replication of the CRAd agent CRAd-survivin was susceptible to a tumor-specific promoter survivin, which was stimulated by the treatment of cisplatin. Thus, the second possibility is of interest in that cisplatin could enhance the viral replication via the stimulation of the activity of the survivin promoter.…”

“…Moreover, the evidence indicated that irradiation and CDDP increased the activity of the survivin promoter in human glioma cell lines. 13,14 However, no trials have been conducted on the tumor cellYkilling effect of the combined therapy with the survivin promoter-based conditionally replicating adenovirus (CRAd-survivin) and chemotherapy in ovarian cancer.…”