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Current Pharmaceutical Biotechnology


ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Differences in the Expression Pattern of mRNA Protein SEMA3F in Endometrial Cancer in vitro under Cisplatin Treatment

Author(s): Przemysław Kieszkowski*, Dariusz Dąbruś, Beniamin O. Grabarek and Dariusz Boroń

Volume 21, Issue 11, 2020

Page: [1119 - 1128] Pages: 10

DOI: 10.2174/1389201021666200416102540

open access plus


Background: Semaphorin 3F (SEMA3F) plays a substantial role in carcinogenesis, because of its role in inducing angiogenesis, and creating a microenvironment for the developing tumor.

Objective: The purpose of this work was to assess the impact of cisplatin, depending on the concentration and exposure time on the expression pattern of SEMA3F in an endometrial cancer cell line.

Materials and Methods: Cultures of the Ishikawa endometrial cancer cells were incubated with cisplatin with the following concentrations: 2.5μM; 5μM; and 10μM and for the following periods of time: 12; 24; and 48 hours. Cells not incubated with the drug constituted the control in the experiment. To determine the effect of cisplatin on the expression of SEMA3F, the real-time quantitative reverse transcription reaction (RtqPCR; mRNA) was used, as well as the ELISA assay (protein). The statistical analysis was done with the admission of p<0.05.

Results: The silencing of SEMA3F expression on the transcriptome and proteome levels in a culture unexposed to the effects of cisplatin in comparison to endometrial cancer cells under the influence of cisplatin (p<0.05) were noted. Along with an increase in the concentration of the drug used, the number of copies of the gene transcript, during the shortest incubation period had a gradual increase. Only for the highest concentration of the drug, substantial statistical differences in the expression of the SEMA3F protein between 24 and 48 hour incubation periods (p<0.05) were determined.

Conclusion: Using cisplatin in an endometrial cancer cell culture results in an increased expression of SEMA3F, which advantageously affects the normalization of the neoplastic angiogenic process and lowers the proliferation of the cells making up the mass of the tumor.

Keywords: SEMA3F, endometrial cancer cell line, cisplatin, expression, supplementary molecular marker, gene transcript.

Graphical Abstract
Franzolin, G.; Tamagnone, L. Semaphorin signaling in cancer-associated inflammation. Int. J. Mol. Sci., 2019, 20(2), 377.
[] [PMID: 30658382]
Toledano, S.; Nir-Zvi, I.; Engelman, R.; Kessler, O.; Neufeld, G. Class-3 semaphorins and their receptors: Potent multifunctional modulators of tumor progression. Int. J. Mol. Sci., 2019, 20(3), 556.
[] [PMID: 30696103]
Junqueira Alves, C.; Yotoko, K.; Zou, H.; Friedel, R.H. Origin and evolution of plexins, semaphorins, and Met receptor tyrosine kinases. Sci. Rep., 2019, 9(1), 1970.
[] [PMID: 30760850]
Reinartz, S.; Finkernagel, F.; Adhikary, T.; Rohnalter, V.; Schumann, T.; Schober, Y.; Nockher, W.A.; Nist, A.; Stiewe, T.; Jansen, J.M.; Wagner, U.; Müller-Brüsselbach, S.; Müller, R. A transcriptome-based global map of signaling pathways in the ovarian cancer microenvironment associated with clinical outcome. Genome Biol., 2016, 17(1), 108.
[] [PMID: 27215396]
Wong, L.L.; Lee, N.G.; Amarnani, D.; Choi, C.J.; Bielenberg, D.R.; Freitag, S.K.; D’Amore, P.A.; Kim, L.A. Orbital angiogenesis and lymphangiogenesis in thyroid eye disease: An analysis of vascular growth factors with clinical correlation. Ophthalmology, 2016, 123(9), 2028-2036.
[] [PMID: 27423310]
Doçi, C.L.; Mikelis, C.M.; Lionakis, M.S.; Molinolo, A.A.; Gutkind, J.S. Genetic identification of SEMA3F as an antilymphangiogenic metastasis suppressor gene in head and neck squamous carcinoma. Cancer Res., 2015, 75(14), 2937-2948.
[] [PMID: 25952650]
Wu, F.; Zhou, Q.; Yang, J.; Duan, G.J.; Ou, J.J.; Zhang, R.; Pan, F.; Peng, Q.P.; Tan, H.; Ping, Y.F.; Cui, Y.H.; Qian, C.; Yan, X.C.; Bian, X.W. Endogenous axon guiding chemorepulsant semaphorin-3F inhibits the growth and metastasis of colorectal carcinoma. Clin. Cancer Res., 2011, 17(9), 2702-2711.
[] [PMID: 21349996]
Kigel, B.; Varshavsky, A.; Kessler, O.; Neufeld, G. Successful inhibition of tumor development by specific class-3 semaphorins is associated with expression of appropriate semaphorin receptors by tumor cells. PLoS One, 2008, 3(9), e3287.
[] [PMID: 18818766]
Guo, H.F.; Li, X.; Parker, M.W.; Waltenberger, J.; Becker, P.M.; Vander Kooi, C.W. Mechanistic basis for the potent anti-angiogenic activity of semaphorin 3F. Biochemistry, 2013, 52(43), 7551-7558.
[] [PMID: 24079887]
Parker, M.W.; Hellman, L.M.; Xu, P.; Fried, M.G.; Vander Kooi, C.W. Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin. Biochemistry, 2010, 49(19), 4068-4075.
[] [PMID: 20387901]
Guttmann-Raviv, N.; Shraga-Heled, N.; Varshavsky, A.; Guimaraes-Sternberg, C.; Kessler, O.; Neufeld, G. Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis. J. Biol. Chem., 2007, 282(36), 26294-26305.
[] [PMID: 17569671]
Bielenberg, D.R.; Hida, Y.; Shimizu, A.; Kaipainen, A.; Kreuter, M.; Kim, C.C.; Klagsbrun, M. Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype. J. Clin. Invest., 2004, 114(9), 1260-1271.
[] [PMID: 15520858]
Medico, E.; Russo, M.; Picco, G.; Cancelliere, C.; Valtorta, E.; Corti, G.; Buscarino, M.; Isella, C.; Lamba, S.; Martinoglio, B.; Veronese, S.; Siena, S.; Sartore-Bianchi, A.; Beccuti, M.; Mottolese, M.; Linnebacher, M.; Cordero, F.; Di Nicolantonio, F.; Bardelli, A. The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets. Nat. Commun., 2015, 6, 7002.
[] [PMID: 25926053]
Rodriguez-Freixinos, V.; Ruiz-Pace, F.; Fariñas-Madrid, L.; Garrido-Castro, A.C.; Villacampa, G.; Nuciforo, P.; Dienstmann, R.; Vivancos, A. Genomic heterogeneity and efficacy of PI3K pathway inhibitors in patients with gynaecological cancer. ESMO open Cancer Horizons, 2019, 4(2), e000444.
Kölbl, A.C.; Birk, A.E.; Kuhn, C.; Jeschke, U.; Andergassen, U. Influence of VEGFR and LHCGR on endometrial adenocarcinoma. Oncol. Lett., 2016, 12(3), 2092-2098.
[] [PMID: 27625708]
Randall, M.E.; Filiaci, V.L.; Muss, H.; Spirtos, N.M.; Mannel, R.S.; Fowler, J.; Thigpen, J.T.; Benda, J.A. Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. J. Clin. Oncol., 2006, 24(1), 36-44.
[] [PMID: 16330675]
Manohar, S.; Leung, N. Cisplatin nephrotoxicity: A review of the literature. J. Nephrol., 2018, 31(1), 15-25.
[] [PMID: 28382507]
Beuten, J.; Garcia, D.; Brand, T.C.; He, X.; Balic, I.; Canby-Hagino, E.; Troyer, D.A.; Baillargeon, J.; Hernandez, J.; Thompson, I.M.; Leach, R.J.; Naylor, S.L. Semaphorin 3B and 3F single nucleotide polymorphisms are associated with prostate cancer risk and poor prognosis. J. Urol., 2009, 182(4), 1614-1620.
[] [PMID: 19683737]
Li, K.; Chen, M.K.; Li, L.Y.; Lu, M.H.; Shao, C.; Su, Z.L.; Gao, X. The predictive value of semaphorins 3 expression in biopsies for biochemical recurrence of patients with low-and intermediate-risk prostate cancer. Neoplasma, 2013, 60(6), 683-689.
[] [PMID: 23906303]
Drenberg, C.D.; Livingston, S.; Chen, R.; Kruk, P.A.; Nicosia, S.V. Expression of semaphorin 3F and its receptors in epithelial ovarian cancer, fallopian tubes, and secondary Müllerian tissues. Obstet. Gynecol. Int., 2009, 2009, 730739.
[] [PMID: 20041133]
Soleimani, A.; Khazaei, M.; Ferns, G.A.; Ryzhikov, M.; Avan, A.; Hassanian, S.M. Role of TGF-β signaling regulatory microRNAs in the pathogenesis of colorectal cancer. J. Cell. Physiol., 2019, 234(9), 14574-14580.
[] [PMID: 30684274]
Nishida, M.; Kasahara, K.; Oki, A.; Satoh, T.; Arai, Y.; Kubo, T. Establishment of eighteen clones of Ishikawa cells. Hum. Cell, 1996, 9(2), 109-116.
[PMID: 9183638]
Jiang, H.; Qi, L.; Wang, F.; Sun, Z.; Huang, Z.; Xi, Q. Decreased semaphorin 3A expression is associated with a poor prognosis in patients with epithelial ovarian carcinoma. Int. J. Mol. Med., 2015, 35(5), 1374-1380.
[] [PMID: 25812535]
Michalska-Bańkowska, A.; Wcisło-Dziadecka, D.; Grabarek, B.; Brzezińska-Wcisło, L.; Mazurek, U.; Salwowska, N.; Bańkowski, M. Variances in the mRNA expression profile of TGF-β1–3 isoforms and its TGF-βRI–III receptors during cyclosporin a treatment of psoriatic patients. Adv. Dermatol. Allergology, 2018, 35(5), 502.
Grabarek, B.; Wcisło-Dziadecka, D.; Strzałka-Mrozik, B.; Adamska, J.; Mazurek, U.; Brzezińska-Wcisło, L. The capability to forecast response to therapy with regard to the time and intensity of the inflammatory process in vitro in dermal fibroblasts induced by IL-12. Curr. Pharm. Biotechnol., 2018, 19(15), 1232-1240.
[] [PMID: 30636601]
Galluzzi, L.; Senovilla, L.; Vitale, I.; Michels, J.; Martins, I.; Kepp, O.; Castedo, M.; Kroemer, G. Molecular mechanisms of cisplatin resistance. Oncogene, 2012, 31(15), 1869-1883.
[] [PMID: 21892204]
Florea, A.M.; Büsselberg, D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel), 2011, 3(1), 1351-1371.
[] [PMID: 24212665]
Bélanger, F.; Fortier, E.; Dubé, M.; Lemay, J.F.; Buisson, R.; Masson, J.Y.; Elsherbiny, A.; Costantino, S.; Carmona, E.; Mes-Masson, A.M.; Wurtele, H.; Drobetsky, E. Replication protein A availability during DNA replication stress is a major determinant of cisplatin resistance in ovarian cancer cells. Cancer Res., 2018, 78(19), 5561-5573.
[] [PMID: 30072396]
Ottes Vasconcelos, R.; Serini, S.; de Souza Votto, A.P.; Santos Trindade, G.; Fanali, C.; Sgambato, A.; Calviello, G.; Calviello, G. Combination of ω-3 fatty acids and cisplatin as a potential alternative strategy for personalized therapy of metastatic melanoma: an in-vitro study. Melanoma Res., 2019, 29(3), 270-280.
[] [PMID: 30550405]
Moran, M.S. Advancements and personalization of breast cancer treatment strategies in radiation therapy. Optimizing Breast Cancer Management; Springer: Cham, 2018.
Mittra, A.; Moscow, J.A. Future approaches to precision oncology-based clinical trials. Cancer J., 2019, 25(4), 300-304.
[] [PMID: 31335395]
Kohei, N.; Sugiyama, K.; Chihara, I.; Muro, Y.; Imamura, M.; Nishio, Y.; Yoshimura, K. Impact of relative dose intensity in gemcitabine-cisplatin chemotherapy for metastatic urothelial carcinoma. SAGE Open Med., 2018.62050312118783011
[] [PMID: 30013781]
Yamada, Y.; Boku, N.; Mizusawa, J.; Iwasa, S.; Kadowaki, S.; Nakayama, N.; Azuma, M.; Sakamoto, T.; Shitara, K.; Tamura, T.; Chin, K.; Hata, H.; Nakamori, M.; Hara, H.; Yasui, H.; Katayama, H.; Fukuda, H.; Yoshikawa, T.; Sasako, M.; Terashima, M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): An open-label, phase 3, randomised controlled trial. Lancet Gastroenterol. Hepatol., 2019, 4(7), 501-510.
[] [PMID: 31101534]
Mondal, J.; Bishayee, K.; Panigrahi, A.K.; Khuda-Bukhsh, A.R. Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro. J. Integr. Med., 2014, 12(5), 425-438.
[] [PMID: 25292342]
Shen, S.J.; Zhang, Y.H.; Gu, X.X.; Jiang, S.J.; Xu, L.J. Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway. J. Integr. Med., 2017, 15(3), 242-251.
[] [PMID: 28494854]
Nguyen, H.; Ivanova, V.S.; Kavandi, L.; Rodriguez, G.C.; Maxwell, G.L.; Syed, V. Progesterone and 1,25-dihydroxyvitamin D3 inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Mol. Cancer Res., 2011, 9(11), 1479-1492.
[] [PMID: 21933904]
Scheerer, C.; Frangini, S.; Chiantera, V.; Mechsner, S. reduced sympathetic innervation in endometriosis is associated to semaphorin 3C and 3F expression. Mol. Neurobiol., 2017, 54(7), 5131-5141.
[] [PMID: 27558236]
Dziobek, K.; Opławski, M.; Grabarek, B.; Zmarzły, N.; Kiełbasiński, R.; Leśniak, E.; Januszyk, P.; Januszyk, K.; Adwent, I.; Dąbruś, D.; Kieszkowski, P.; Kiełbasiński, K.; Kuś-Kierach, A.; Boroń, D. Changes in expression pattern of SEMA3F depending on endometrial cancer grade - pilot study. Curr. Pharm. Biotechnol., 2019, 20(9), 727-732.
[] [PMID: 31215376]
Holinka, C.F.; Hata, H.; Kuramoto, H.; Gurpide, E. Responses to estradiol in a human endometrial adenocarcinoma cell line (Ishikawa). J. Steroid Biochem., 1986, 24(1), 85-89.
[] [PMID: 3702430]
Parkes, C.; Kamal, A.; Valentijn, A.J.; Alnafakh, R.; Gross, S.R.; Barraclough, R.; Moss, D.; Kirwan, J.; Hapangama, D.K. Assessing estrogen-induced proliferative response in an endometrial cancer cell line using a universally applicable methodological guide. Int. J. Gynecol. Cancer, 2018, 28(1), 122-133.
[] [PMID: 28953135]
Richeri, A.; Chalar, C.; Martínez, G.; Greif, G.; Bianchimano, P.; Brauer, M.M. Estrogen up-regulation of semaphorin 3F correlates with sympathetic denervation of the rat uterus. Auton. Neurosci., 2011, 164(1-2), 43-50.
[] [PMID: 21724473]
Edjekouane, L.; Benhadjeba, S.; Jangal, M.; Fleury, H.; Gévry, N.; Carmona, E.; Tremblay, A. Proximal and distal regulation of the HYAL1 gene cluster by the estrogen receptor α in breast cancer cells. Oncotarget, 2016, 7(47), 77276-77290.
[] [PMID: 27764788 ]

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