Effects of shRNA Expression Vector-mediated Glutathione S-transferase P1 Gene Silencing on Prostate Cancer DU145 Cells
American Journal of Clinical and Experimental Medicine
Volume 7, Issue 5, September 2019, Pages: 119-125
Received: Sep. 23, 2019;
Published: Nov. 18, 2019
Views 616 Downloads 168
Ruirui Xu, Department of Nephrology, Binzhou People's Hospital, Binzhou City, P. R. China
Zhufu Shao, Department of Critical Care Medicine, Binzhou People's Hospital, Binzhou City, P. R. China
Zhi Xiao, Department of Nephrology, Binzhou People's Hospital, Binzhou City, P. R. China
Objective: This study aims to explore the impact of silent GSTP1 gene on the proliferation activity, cell cycle and apoptotic rate of the androgen-independent prostate cancer cell strain DU145. Methods: Thirty subjects with benign prostatic hyperplasia (BPH) who had been subject to urinary surgical resection and pathological diagnosis, 30 subjects with radically cured prostate cancer (PCa), and another 30 subjects with hormone refractory prostate cancer (HRPC) were enrolled. The GSTP1 expression in the subjects was tested with the immunohistochemical S-P method, the GSTP1 expression in the blood serum of the patients with prostatic hyperplasia and prostate cancer was tested with Elisa, and the mRNA level of the GSTP1 gene after the DUl45 cells were transfected with shRNA was tested. Results: Four of the HRPC patients were complicated with bone metastasis, two with bladder invasion, and five with liver and lung metastasis. GSTP1 showed high expression in tissues with prostatic hyperplasia and hormone refractory prostate cancer and low expression in tissues with prostate cancer, and the differences were statistically significant (P<0.05). Difference was found among the serum concentrations of the BPH group, the PCa group and the HRPC group. The HRPC group showed serum GSTP1 concentration higher than that of the PCa group (P<0.01), the BPH group also showed serum GSTP1 concentration higher than that of the PCa group (P<0.01), and the difference between the serum concentrations of the BPH group and the HRPC group was not statistically significant (P>0.05). The GSTP1 mRNA content decreased significantly after shRNA554 intervention, with an IOD value of 67.1±8.7. The intervention effect was evidently lower than that of the carrier shRNA255 group (162.2±12.6) and the shRNA593 group (114.5±10.6) with statistically significant difference (P<0.01). Conclusion: The expression vector-mediated GSTP1-shRNA554 transfection can reduce the mRNA level of the GSTP1 gene of the androgen-independent prostate cancer DU145 cells and inhibit the proliferation activity of the in vitro cultivated DU145 cells.
Effects of shRNA Expression Vector-mediated Glutathione S-transferase P1 Gene Silencing on Prostate Cancer DU145 Cells, American Journal of Clinical and Experimental Medicine.
Vol. 7, No. 5,
2019, pp. 119-125.
Chung SD. Liu SP. et al. Association between Prostate Cancer and Urinary Calculi: A Population-Based Study [J]. PLoS One, 2019, 8 (2): 743-6.
Mo Z. Gao Y. et al. An updating meta-analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: a HuGE review [J]. Prostate, 2009, 69 (6): 662-88.
Weroha SJ. Quevedo JF. et al. Treatment of hormone-refractory prostate cancer, HRPC, remains challenging [J]. Med Oncol, 2016, 27 (2): 569-71.
Malakar M. Devi KR. et al. Genetic polymorphism of glutathione S-transferases M1 and T1, tobacco habits and risk of stomach cancer in Mizoram, India [J]. Asian Pac J Cancer Prev, 2018, 13 (9): 4725-32.
Luo W. Kinsey M. et al. Glutathione s-transferases in pediatric cancer [J]. Front Oncol, 2017, 1 (39): 249-52.
Jin P. Xie J. et al. Effect of gene GSTP1 silencing via shRNA transfection on androgen independent prostate cancer cell line Du145 [J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2018, 37 (8): 807-16.
Gong M. Dong W. et al. Genetic polymorphisms of GSTM1, GSTT1, and GSTP1 with prostate cancer risk: a meta-analysis of 57 studies [J]. PLoS One, 2018, 7 (11): 587-9.
Leite KR. Srougi M. et al. The use of immunohistochemistry for diagnosis of prostate cancer [J]. Int Braz J Urol, 2016, 36 (5): 583-90.
Chiam K. Centenera MM. et al. GSTP1 DNA methylation and expression status is indicative of 5-aza-2'-deoxycytidine efficacy in human prostate cancer cells [J]. PLoS One, 2017, 6 (9): 634-6.
Yoon HY. Kim SK. et al. Combined hypermethylation of APC and GSTP1 as a molecular marker for prostate cancer: quantitative pyrosequencing analysis [J]. J Biomol Screen, 2018, 17 (7): 987-92.
Qadri Q. Sameer AS. et al. Genetic polymorphism of the glutathione-S-transferase P1 gene (GSTP1) and susceptibility to prostate cancer in the Kashmiri population [J]. Genet Mol Res, 2017, 10 (4): 3038-45.
Zhao Y. Wang F. et al. Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - a meta-analysis [J]. Int J Med Sci, 2016, 7 (5): 300-8.
Re A. Aiello A. et al. Silencing of GSTP1, a prostate cancer prognostic gene, by the estrogen receptor-beta and endothelial nitric oxide synthase complex [J]. Mol Endocrinol, 2017, 25 (12): 2003-16.
Hauptstock V. Kuriakose S. et al. Glutathione-S-transferase pi 1 (GSTP1) gene silencing in prostate cancer cells is reversed by the histone deacetylase inhibitor depsipeptide [J]. Biochem Biophys Res Commun, 2017, 412 (4): 606-11.
Syeed N. Syed Sameer A. et al. Promoter methylation profile of GSTP1 and RASSF1A in benign hyperplasia and metastatic prostate cancer patients in a Kashmiri population [J]. Mol Med Rep, 2017, 3 (5): 883-7.
Kiran B. Karkucak M. et al. GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer [J]. J Gynecol Oncol, 2016, 21 (3): 169-73.
Wang J. Zhang J. et al. Expression of P-gp, MRP, LRP, GST-pi and TopoIIalpha and intrinsic resistance in human lung cancer cell lines [J]. Oncol Rep, 2017, 26 (5): 1081-9.
Lu D. Shi HC. et al. Multidrug resistance-associated biomarkers PGP, GST-pi, Topo-II and LRP as prognostic factors in primary ovarian carcinoma [J]. Br J Biomed Sci, 2017, 68 (2): 69-74.
Zhang Y. Liu J. et al. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants [J]. J Hazard Mater, 2017, 189 (2): 357-62.
Hasegawa K. Miwa S. et al. Allyl isothiocyanate that induces GST and UGT expression confers oxidative stress resistance on C. elegans, as demonstrated by nematode biosensor [J]. PLoS One, 2016, 5 (2): 267-9.
Bai YL. Zhou B. et al. Predictive role of GSTs on the prognosis of breast cancer patients with neoadjuvant chemotherapy [J]. Asian Pac J Cancer Prev, 2018, 13 (10): 5019-22.
Richiardi L. Fiano V. et al. Promoter methylation in APC, RUNX3, and GSTP1 and mortality in prostate cancer patients [J]. J Clin Oncol, 2009, 27 (19): 3161-8.
Pandey M. Shukla S. et al. Promoter demethylation and chromatin remodeling by green tea polyphenols leads to re-expression of GSTP1 in human prostate cancer cells [J]. Int J Cancer, 2016, 126 (11): 2520-33.
Vardi A. Bosviel R. et al. Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells [J]. In Vivo, 2016, 24 (4): 393-400.