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Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary Research

SOX17 increases the cisplatin sensitivity of an endometrial cancer cell line

Authors: Yongli Zhang, FeiZhou Jiang, Wei Bao, Huilin Zhang, XiaoYing He, Huihui Wang, Xiaoping Wan

Published in: Cancer Cell International | Issue 1/2016

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Abstract

Background

Endometrial 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.

Methods

Immunohistochemistry 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.

Results

SOX17 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.

Conclusions

SOX17 is involved in the p53-mediated apoptosis pathway, and increases the sensitivity of HEC-1B cells to cisplatin.
Appendix
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Literature
2.
go back to reference Loukovaara M, Luomaranta A, Leminen A. Treatment of endometrial carcinoma. Duodecim. 2014;130(22–23):2348–55.PubMed Loukovaara M, Luomaranta A, Leminen A. Treatment of endometrial carcinoma. Duodecim. 2014;130(22–23):2348–55.PubMed
3.
go back to reference Sasaki H, Sheng Y, Kotsuji F, Tsang BK. Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res. 2000;60(20):5659–66.PubMed Sasaki H, Sheng Y, Kotsuji F, Tsang BK. Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res. 2000;60(20):5659–66.PubMed
4.
go back to reference Ali AY, Abedini MR, Tsang BK. The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation. Oncogene. 2012;31(17):2175–86.CrossRefPubMed Ali AY, Abedini MR, Tsang BK. The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation. Oncogene. 2012;31(17):2175–86.CrossRefPubMed
5.
go back to reference Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, et al. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990;346(6281):245–50.CrossRefPubMed Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, et al. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990;346(6281):245–50.CrossRefPubMed
6.
go back to reference Jia Y, Yang Y, Brock MV, Zhan Q, Herman JG, Guo M. Epigenetic regulation of DACT2, a key component of the Wnt signalling pathway in human lung cancer. J Pathol. 2013;230(2):194–204.CrossRefPubMedPubMedCentral Jia Y, Yang Y, Brock MV, Zhan Q, Herman JG, Guo M. Epigenetic regulation of DACT2, a key component of the Wnt signalling pathway in human lung cancer. J Pathol. 2013;230(2):194–204.CrossRefPubMedPubMedCentral
7.
go back to reference Katoh M. Molecular cloning and characterization of human SOX17. Int J Mol Med. 2002;9(2):153–7.PubMed Katoh M. Molecular cloning and characterization of human SOX17. Int J Mol Med. 2002;9(2):153–7.PubMed
8.
go back to reference Markowska A, Pawalowska M, Lubin J, Markowska J. Signalling pathways in endometrial cancer. Contemp Oncol (Pozn). 2014;18(3):143–8. Markowska A, Pawalowska M, Lubin J, Markowska J. Signalling pathways in endometrial cancer. Contemp Oncol (Pozn). 2014;18(3):143–8.
9.
go back to reference Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16(1):8–13.PubMed Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16(1):8–13.PubMed
10.
go back to reference Lax SF, Kendall B, Tashiro H, Slebos RJ, Hedrick L. The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer. 2000;88(4):814–24.CrossRefPubMed Lax SF, Kendall B, Tashiro H, Slebos RJ, Hedrick L. The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer. 2000;88(4):814–24.CrossRefPubMed
11.
go back to reference Ragni N, Ferrero S, Prefumo F, Muschiato B, Gorlero F, Gualco M, et al. The association between p53 expression, stage and histological features in endometrial cancer. Eur J Obstet Gynecol Reprod Biol. 2005;123(1):111–6.CrossRefPubMed Ragni N, Ferrero S, Prefumo F, Muschiato B, Gorlero F, Gualco M, et al. The association between p53 expression, stage and histological features in endometrial cancer. Eur J Obstet Gynecol Reprod Biol. 2005;123(1):111–6.CrossRefPubMed
12.
go back to reference Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11(3):577–90.CrossRefPubMed Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11(3):577–90.CrossRefPubMed
13.
go back to reference Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C, et al. WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem. 2006;281(3):8600–6.CrossRefPubMed Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C, et al. WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem. 2006;281(3):8600–6.CrossRefPubMed
14.
go back to reference Yang L, Zhou Y, Li Y, Zhou J, Wu Y, Cui Y, et al. Mutations of p53 and KRAS activate NF-κB to promote chemoresistance and tumorigenesis via dysregulation of cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett. 2015;357(2):520–6.CrossRefPubMed Yang L, Zhou Y, Li Y, Zhou J, Wu Y, Cui Y, et al. Mutations of p53 and KRAS activate NF-κB to promote chemoresistance and tumorigenesis via dysregulation of cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett. 2015;357(2):520–6.CrossRefPubMed
15.
go back to reference Li B, Gao Y, Rankin GO, Rojanasakul Y, Cutler SJ, Tu Y, et al. Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells. Cancer Lett. 2015;356(2 Pt B):418–33.CrossRefPubMedPubMedCentral Li B, Gao Y, Rankin GO, Rojanasakul Y, Cutler SJ, Tu Y, et al. Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells. Cancer Lett. 2015;356(2 Pt B):418–33.CrossRefPubMedPubMedCentral
16.
go back to reference Conway K, Edmiston SN, May R, Kuan PF, Chu H, Bryant C, et al. DNA methylation profiling in the Carolina breast cancer study defines cancer subclasses differing in clinicopathologic characteristics and survival. Breast Cancer Res. 2014;16(5):450.CrossRefPubMedPubMedCentral Conway K, Edmiston SN, May R, Kuan PF, Chu H, Bryant C, et al. DNA methylation profiling in the Carolina breast cancer study defines cancer subclasses differing in clinicopathologic characteristics and survival. Breast Cancer Res. 2014;16(5):450.CrossRefPubMedPubMedCentral
17.
go back to reference Liu Ying, Ren Zhonghai, Shuning Xu, Bai Hua, Ma Ning, Wang Feng. Low-dose-intensity bevacizumab with weekly irinotecan for platinum-and taxanes-resistant epithelial ovarian cancer. Cancer Chemother Pharmacol. 2015;75(3):645–51.CrossRefPubMedPubMedCentral Liu Ying, Ren Zhonghai, Shuning Xu, Bai Hua, Ma Ning, Wang Feng. Low-dose-intensity bevacizumab with weekly irinotecan for platinum-and taxanes-resistant epithelial ovarian cancer. Cancer Chemother Pharmacol. 2015;75(3):645–51.CrossRefPubMedPubMedCentral
18.
go back to reference Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, et al. Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem. 1998;273(42):27084–90.CrossRefPubMed Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, et al. Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem. 1998;273(42):27084–90.CrossRefPubMed
19.
20.
go back to reference Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305(5684):626–9.CrossRefPubMed Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305(5684):626–9.CrossRefPubMed
21.
go back to reference Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA. 1998;95(9):4997–5002.CrossRefPubMedPubMedCentral Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA. 1998;95(9):4997–5002.CrossRefPubMedPubMedCentral
22.
go back to reference Yuan G, Regel I, Lian F, Friedrich T, Hitkova I, Hofheinz RD, et al. WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells. Oncogene. 2013;32(3):375–87.CrossRefPubMed Yuan G, Regel I, Lian F, Friedrich T, Hitkova I, Hofheinz RD, et al. WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells. Oncogene. 2013;32(3):375–87.CrossRefPubMed
23.
go back to reference Drayton RM, Catto JW. Molecular mechanisms of cisplatin resistance in bladder cancer. Expert Rev Anticancer Ther. 2012;12(2):271–81.CrossRefPubMed Drayton RM, Catto JW. Molecular mechanisms of cisplatin resistance in bladder cancer. Expert Rev Anticancer Ther. 2012;12(2):271–81.CrossRefPubMed
25.
go back to reference Han F, Liu W, Jiang X, Shi X, Yin L, Ao L, et al. SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer. Oncogene. 2015;34(33):4391–402.CrossRefPubMedPubMedCentral Han F, Liu W, Jiang X, Shi X, Yin L, Ao L, et al. SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer. Oncogene. 2015;34(33):4391–402.CrossRefPubMedPubMedCentral
26.
go back to reference Sherman ME, Bur ME, Kurman RJ. p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol. 1995;26(11):1268–74.CrossRefPubMed Sherman ME, Bur ME, Kurman RJ. p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol. 1995;26(11):1268–74.CrossRefPubMed
27.
go back to reference Feng YZ, Shiozawa T, Horiuchi A, Shih HC, Miyamoto T, Kashima H, et al. Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas. Virchows Arch. 2005;447(5):816–22.CrossRefPubMed Feng YZ, Shiozawa T, Horiuchi A, Shih HC, Miyamoto T, Kashima H, et al. Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas. Virchows Arch. 2005;447(5):816–22.CrossRefPubMed
28.
go back to reference Tang X, Hu G, Xu C, Ouyang K, Fang W, Huang W, et al. HZ08 reverse the aneuploidy-induced cisplatin-resistance in Gastric cancer by modulating the p53 pathway. Eur J Pharmacol. 2013;720(1–3):84–97.CrossRefPubMed Tang X, Hu G, Xu C, Ouyang K, Fang W, Huang W, et al. HZ08 reverse the aneuploidy-induced cisplatin-resistance in Gastric cancer by modulating the p53 pathway. Eur J Pharmacol. 2013;720(1–3):84–97.CrossRefPubMed
29.
go back to reference Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009;105(2):109.CrossRefPubMed Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009;105(2):109.CrossRefPubMed
30.
go back to reference Xu N, Shen C, Luo Y, Xia L, Xue F, Xia Q, et al. Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell. Biochem Biophys Res Commun. 2012;425(2):468–72.CrossRefPubMed Xu N, Shen C, Luo Y, Xia L, Xue F, Xia Q, et al. Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell. Biochem Biophys Res Commun. 2012;425(2):468–72.CrossRefPubMed
31.
go back to reference Xue X, Gao W, Sun B, Xu Y, Han B, Wang F, et al. Vasohibin 2 is transcriptionally activated and promotes angiogenesis in hepatocellular carcinoma. Oncogene. 2013;32(13):1724–34.CrossRefPubMed Xue X, Gao W, Sun B, Xu Y, Han B, Wang F, et al. Vasohibin 2 is transcriptionally activated and promotes angiogenesis in hepatocellular carcinoma. Oncogene. 2013;32(13):1724–34.CrossRefPubMed
32.
go back to reference Wang F, Li X, Xie X, Zhao L, Chen W. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 2008;582(13):1919–27.CrossRefPubMed Wang F, Li X, Xie X, Zhao L, Chen W. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 2008;582(13):1919–27.CrossRefPubMed
Metadata
Title
SOX17 increases the cisplatin sensitivity of an endometrial cancer cell line
Authors
Yongli Zhang
FeiZhou Jiang
Wei Bao
Huilin Zhang
XiaoYing He
Huihui Wang
Xiaoping Wan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0304-7

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