Abstract
BackgroundEndometrial cancer (EC) is the most common form of malignant gynecological tumor. Treatment with cisplatin (CDDP) is the mainstay of EC chemotherapy. The apoptotic machinery is regarded as an important etiological factor in chemoresistance. Recent evidence has suggested that overexpression of the transcription factor SOX17 prevented apoptosis in tumor cell lines. The effect of SOX17 on apoptosis in EC cisplatin chemoresistance remains unclear.MethodsImmunohistochemistry and the reverse transcription-polymerase chain reaction were employed to detect gene expression in paraffin-embedded EC tissues and blood samples. The anti-proliferative ability of SOX17 on EC cells was assessed by MTT. Flow cytometric analysis was used to detect cell apoptosis by annexin V/PI double-staining. The expression of apoptosis-related proteins was analyzed by western blot. In the in vivo study, nude mice were subcutaneously injected with EC cells, and received cisplatin treatment through intraperitoneal chemotherapy. Apoptosis of in vivo samples was analyzed by TUNEL assay.ResultsSOX17 expression decreased the chemical resistance of EC cells to CDDP. HEC-1B cells with an elevated expression of SOX17 had a lower cell viability and higher apoptosis rate after cisplatin exposure. Overexpression SOX17 up-regulated wild type p53 after being exposed to cisplatin, while the expression of BCL2-associated X protein and cleaved caspase-3 simultaneously increased. Caspase-9 inhibitor reduced the efficacy of SOX17 in HEC-1B cells after cisplatin treatment. In the in vivo study, SOX17 overexpression clearly restrained the tumor growth and increased the cisplatin toxicity and apoptosis of tumor cells.ConclusionsSOX17 is involved in the p53-mediated apoptosis pathway, and increases the sensitivity of HEC-1B cells to cisplatin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0304-7) contains supplementary material, which is available to authorized users.
Highlights
Endometrial cancer (EC) is the most common form of malignant gynecological tumor
SOX17 expression is decreased in chemo‐resistant endometrial cancer Patients with EC who have received comprehensive staging surgery and suffered disease relapse within 6 months after regular platinum containing therapy are considered to be platinum resistant [17]
To clarify the molecular mechanisms underlying CDDP resistance in EC cells, SOX17 expression levels in 29 EC patients were assayed after cisplatin-based combination chemotherapy
Summary
Endometrial cancer (EC) is the most common form of malignant gynecological tumor. Treatment with cisplatin (CDDP) is the mainstay of EC chemotherapy. Recent evidence has suggested that overexpression of the transcription factor SOX17 prevented apoptosis in tumor cell lines. The effect of SOX17 on apoptosis in EC cisplatin chemoresistance remains unclear. Endometrial cancer (EC) is the most common form of gynecological malignancy, with an estimated 47,130 new cases and 8010 deaths occurring in 2014 [1]. CDDP is the first-line chemotherapeutic agent for EC treatment. The importance of the transcription factor SOX17 (SRY-box containing gene 17) in EC cell biology has recently aroused great interest. SOX17 belongs to the high mobility group (HMG) box transcription factor superfamily, which is homologous to the sex-determining gene SRY [5].
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