Expression levels of MRP1, GST-π, and GSK3β in ovarian cancer and the relationship with drug resistance and prognosis of patients

Tong,Xiaojing; Zhao,Jiao; Zhang,Yuhua; Mu,Peng; Wang,Xiaobin

doi:10.3892/ol.2019.10315

Expression levels of MRP1, GST-π, and GSK3β in ovarian cancer and the relationship with drug resistance and prognosis of patients

Authors:
- Xiaojing Tong
- Jiao Zhao
- Yuhua Zhang
- Peng Mu
- Xiaobin Wang
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Affiliations: Department of Gynecology, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, Liaoning 110042, P.R. China
Published online on: May 6, 2019 https://doi.org/10.3892/ol.2019.10315
Pages: 22-28
Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Expression levels of multidrug resistance-associated protein 1 (MRP1), glutathione S-transferase π (GST-π) and glycogen synthase kinase-3β (GSK3β) were investigated in ovarian epithelial cancer and the relationship with the primary drug resistance of patients with ovarian cancer to chemotherapy. One hundred and twenty-one ovarian cancer tissue samples from patients who underwent ovarian cancer resection from January 2013 to June 2015 in Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University were enrolled in the Experimental group, while 58 ovarian tissue samples from patients with fallopian tube obstruction but with no ovarian cancer who received surgical treatment for blocked fallopian tube were included in the Control group. After the detection of the expression levels of MRP1, GST-π, and GSK3β mRNA by RT-PCR and the analysis of related clinical pathological factors, patients in the Experimental group were divided into the Chemotherapy‑sensitive and Chemotherapy-resistant groups according to the chemotherapy efficacy. Additionally, with the mean expression levels of MRP1, GST-π, and GSK3β in ovarian cancer tissues as the boundaries, the expression levels of the three genes in the Experimental group were classified into high expression and low expression. Ovarian cancer tissues had much higher expression levels of MRP1, GST-π, and GSK3β mRNA than normal ovarian tissues (P<0.05). The expression levels of MRP1, GST-π, and GSK3β mRNA in the Chemotherapy-sensitive group were significantly lower than those in the Chemotherapy-resistant group (P<0.05). Patients with high expression of MRP1, GST-π, and GSK3β mRNA had a much lower 3-year survival rate than patients with low expression of the genes (P<0.05). Highly expressed in patients with ovarian cancer, MRP1, GST-π, and GSK3β mRNA play an important role in the development and drug resistance of ovarian cancer, which ensures this study is of positive clinical guiding significance in developing proper treatment for ovarian cancer and evaluating the efficacy of chemotherapy.

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1	Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, Amso NN, Apostolidou S, Benjamin E, Cruickshank D, et al: Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. Lancet. 387:945–956. 2016. View Article : Google Scholar : PubMed/NCBI
2	Duran GE, Wang YC, Moisan F, Francisco EB and Sikic BI: Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition. Br J Cancer. 116:1318–1328. 2017. View Article : Google Scholar : PubMed/NCBI
3	Chen FQ, Zhang JM, Fang XF, Yu H, Liu YL, Li H, Wang YT and Chen MW: Reversal of paclitaxel resistance in human ovarian cancer cells with redox-responsive micelles consisting of α-tocopheryl succinate-based polyphosphoester copolymers. Acta Pharmacol Sin. 38:859–873. 2017. View Article : Google Scholar : PubMed/NCBI
4	Wu W, Fan L, Bao Z, Zhang Y, Peng Y, Shao M, Xiang Y, Zhang X, Wang Q and Tao L: The cytoplasmic translocation of Cx32 mediates cisplatin resistance in ovarian cancer cells. Biochem Biophys Res Commun. 487:292–299. 2017. View Article : Google Scholar : PubMed/NCBI
5	Huang ZL, Cao X, Luo RZ, Chen YF, Zhu LC and Wen Z: Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study. Oncol Lett. 11:299–305. 2016. View Article : Google Scholar : PubMed/NCBI
6	Stott W, Campbell S, Franchini A, Blyuss O, Zaikin A, Ryan A, Jones C, Gentry-Maharaj A, Fletcher G, Kalsi J, et al: Sonographers' self-reported visualization of normal postmenopausal ovaries on transvaginal ultrasound is not reliable: Results of expert review of archived images from UKCTOCS. Ultrasound Obstet Gynecol. 51:401–408. 2018. View Article : Google Scholar : PubMed/NCBI
7	Thomas DS, Fourkala EO, Apostolidou S, Gunu R, Ryan A, Jacobs I, Menon U, Alderton W, Gentry-Maharaj A and Timms JF: Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples. Br J Cancer. 113:268–274. 2015. View Article : Google Scholar : PubMed/NCBI
8	Niiro E, Morioka S, Iwai K, Yamada Y, Ogawa K, Kawahara N and Kobayashi H: Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer. Biomed Rep. 8:215–223. 2018.PubMed/NCBI
9	Abdallah EA, Fanelli MF, Souza E Silva V, Machado Netto MC, Gasparini Junior JL, Araújo DV, Ocea LM, Buim ME, Tariki MS, Alves VS, et al: MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer. Int J Cancer. 139:890–898. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yang X, Leslie G, Gentry-Maharaj A, Ryan A, Intermaggio M, Lee A, Kalsi JK, Tyrer J, Gaba F, Manchanda R, et al: Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study. J Med Genet. 55:546–554. 2018. View Article : Google Scholar : PubMed/NCBI
11	Jenkins V, Fallowfield L, Langridge C, Barrett J, Ryan A, Jacobs I, Kilkerr J, Menon U and Farewell V: Psychosocial factors associated with withdrawal from the United Kingdom Collaborative Trial of Ovarian Cancer Screening after 1 episode of repeat screening. Int J Gynecol Cancer. 25:1519–1525. 2015. View Article : Google Scholar : PubMed/NCBI
12	Basak P, Sadhukhan P, Sarkar P and Sil PC: Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicol Rep. 4:306–318. 2017. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Yao HP: Diagnosis and treatment of recurrent ovarian cancer. Zhonghua Fu Chan Ke Za Zhi. 38:659–660. 2003.(In Chinese). PubMed/NCBI
15	Gizzo S, Noventa M, Quaranta M, Vitagliano A, Saccardi C, Litta P and Antona D: A novel hysteroscopic approach for ovarian cancer screening/early diagnosis. Oncol Lett. 13:549–553. 2017. View Article : Google Scholar : PubMed/NCBI
16	Ataie-Kachoie P, Pillai K, Badar S, Akhter J and Morris DL: Monepantel considerably enhances the therapeutic potentials of PEGylated liposomal doxorubicin and gemcitabine in ovarian cancer: In vitro and in vivo studies. Am J Cancer Res. 8:2064–2075. 2018.PubMed/NCBI
17	Qin M, Jin Y, Ma L, Zhang YY and Pan LY: The role of neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer: A systematic review and meta-analysis of randomized controlled trials and observational studies. Oncotarget. 9:8614–8628. 2017.PubMed/NCBI
18	Senft D, Qi J and Ronai ZA: Ubiquitin ligases in oncogenic transformation and cancer therapy. Nat Rev Cancer. 18:69–88. 2018. View Article : Google Scholar : PubMed/NCBI
19	Zhang KG, Qin CY, Wang HQ, Wang JX and Wang QM: The effect of TRAIL on the expression of multidrug resistant genes MDR1, LRP and GST-π in drug-resistant gastric cancer cell SGC7901/VCR. Hepatogastroenterology. 59:2672–2676. 2012.PubMed/NCBI
20	Menon U, McGuire AJ, Raikou M, Ryan A, Davies SK, Burnell M, Gentry-Maharaj A, Kalsi JK, Singh N, Amso NN, et al: The cost-effectiveness of screening for ovarian cancer: Results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Br J Cancer. 117:619–627. 2017. View Article : Google Scholar : PubMed/NCBI
21	Sedláková I, Laco J, Tošner J, Spaček J and Cermáková E: Drug resistance proteins LRP, Pgp, MRP1, MRP3 and MRP5 in ovarian cancer patients. Ceska Gynekol. 78:545–553. 2013.(In Czech). PubMed/NCBI
22	Ji Q and Qiu L: Mechanism study of PEGylated polyester and β-cyclodextrin integrated micelles on drug resistance reversal in MRP1-overexpressed HL60/ADR cells. Colloids Surf B Biointerfaces. 144:203–213. 2016. View Article : Google Scholar : PubMed/NCBI
23	Fallowfield L, Solis-Trapala I, Menon U, Langridge C, May S, Jacobs I and Jenkins V: The effect of ovarian cancer screening on sexual activity and functioning: Results from the UK collaborative trial of ovarian cancer screening RCT. Br J Cancer. 116:1111–1117. 2017. View Article : Google Scholar : PubMed/NCBI
24	Cao DY, Shen K, Yang JX and Guan J: The expression of MRP, GST-pi, Topo IIalpha and COX-2 in epithelial ovarian cancer and its relationship to drug resistance and prognosis. Zhonghua Yi Xue Za Zhi. 87:1738–1741. 2007.(In Chinese). PubMed/NCBI
25	Russell MR, Graham C, D'Amato A, Gentry-Maharaj A, Ryan A, Kalsi JK, Ainley C, Whetton AD, Menon U, Jacobs I, et al: A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours. Br J Cancer. 117:666–674. 2017. View Article : Google Scholar : PubMed/NCBI
26	Beurel E, Kornprobst M, Blivet-Van Eggelpoël MJ, Cadoret A, Capeau J and Desbois-Mouthon C: GSK-3beta reactivation with LY294002 sensitizes hepatoma cells to chemotherapy-induced apoptosis. Int J Oncol. 27:215–222. 2005.PubMed/NCBI
27	Farago M, Dominguez I, Landesman-Bollag E, Xu X, Rosner A, Cardiff RD and Seldin DC: Kinase-inactive glycogen synthase kinase 3beta promotes Wnt signaling and mammary tumorigenesis. Cancer Res. 65:5792–5801. 2005. View Article : Google Scholar : PubMed/NCBI