Vitamin D regulates cell viability, migration and proliferation by suppressing galectin-3 (Gal-3) gene in ovarian cancer cells

Abstract

Vitamin D deficiency is identified as a risk factor for the occurrence and recurrence of ovarian cancer. Galectin-3 (Gal-3) participates in many physiological and pathological processes. In present study, serum vitamin D level was detected using chemiluminescence enzyme immunoassay. Gal-3 expression was examined using real-time polymerase chain reaction (PCR), Western blot and immunocytochemistry analysis. SKOV3 cells viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, the migration of SKOV3 cells was detected using transwell assay, and the proliferation of SKOV3 cells was measured by 3H-thymidine incorporation (3H-TdR). Our study demonstrated that vitamin D levels were lower in 40 ovarian cancer patients: vitamin D deficiency is closely related to the pathogenesis of ovarian cancer. Treatment with vitamin D reduced the migration and proliferation of ovarian cancer cells. Gal-3 was overexpressed in ovarian cancer, which could induce the viability, migration and proliferation ability of ovarian cancer cells, and these effects were abrogated by vitamin D downregulating the expression of Gal-3 gene. Therefore, our results support that vitamin D may suppress Gal-3-induced viability, migration and proliferation ability of ovarian cancer cells, which suggests that the use of vitamin D may have beneficial effects in preventing and treating ovarian cancer.

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References

  1. Abu-Elsaad NM and Elkashef WF 2016 Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells. Can. J. Physiol. Pharmacol. 94 554–562

    CAS  Article  Google Scholar 

  2. Ahmed JH, Makonnen E, Fotoohi A, Yimer G, Seifu D, Assefa M, Tigeneh W, Aseffa A, et al. 2019 Vitamin D status and association of VDR genetic polymorphism to risk of breast cancer in Ethiopia. Nutrients 11 2019

    Article  Google Scholar 

  3. Altundag K 2019 Combined use of vitamin D and omega-3 fatty acid in breast cancer patients might be more beneficial for reducing aromatase inhibitors-associated arthralgia. J. BUON 24 862

    PubMed  Google Scholar 

  4. Bakhru A, Mallinger JB, Buckanovich RJ and Griggs JJ 2010 Casting light on 25-hydroxyvitamin D deficiency in ovarian cancer: a study from the NHANES. Gynecol. Oncol. 119 314–318

    CAS  Article  Google Scholar 

  5. Bi J, Watanabe H, Fujimura R, Nishida K, Nakamura R, Oshiro S, Imafuku T, Komori H, et al. 2018 A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis. Sci. Rep. 8 17329

    Article  Google Scholar 

  6. Bull CJ, Yarmolinsky J and Wade KH 2016 Commentary: Mendelian randomization analysis identifies circulating vitamin D as a causal risk factor for ovarian cancer. Int. J. Epidemiol 45 1631–1633

    Article  Google Scholar 

  7. Bustos SO, da Silva Pereira GJ, de Freitas Saito R, Gil CD, Zanatta DB, Smaili SS and Chammas R 2018 Galectin-3 sensitized melanoma cell lines to vemurafenib (PLX4032) induced cell death through prevention of autophagy. Oncotarget 9 14567–14579

    Article  Google Scholar 

  8. Cai L, Luo L, Tang Z and Meng X 2018 Combined antitumor effects of 1,25-dihydroxy vitamin D3 and Notch inhibitor in liver cancer. Oncol. Rep. 40 1515–1524

    CAS  PubMed  Google Scholar 

  9. Ceran MU, Tasdemir U, Colak E and Güngör T 2019 Can complete blood count inflammatory parameters in epithelial ovarian cancer contribute to prognosis? - a survival analysis. J. Ovarian Res. 12 16

    Article  Google Scholar 

  10. Chang SW and Lee HC 2019 Vitamin D and health—The missing vitamin in humans. Pediatr. Neonatol. 60 237–244

    Article  Google Scholar 

  11. Cho H, Kim JY and Oh YL 2018 Diagnostic value of HBME-1, CK19, Galectin 3, and CD56 in the subtypes of follicular variant of papillary thyroid carcinoma. Pathol. Int. 68 605–613

    CAS  Article  Google Scholar 

  12. Clark MC, Pang M, Hsu DK, Liu FT, de Vos S, Gascoyne RD, Said J and Baum LG 2012 Galectin-3 binds to CD45 on diffuse large B-cell lymphoma cells to regulate susceptibility to cell death. Blood 120 4635–4644

    CAS  Article  Google Scholar 

  13. Coppin L, Vincent A, Frénois F, Duchêne B, Lahdaoui F, Stechly L, Renaud F, Villenet C, et al. 2017 Galectin-3 is a non-classic RNA binding protein that stabilizes the mucin MUC4 mRNA in the cytoplasm of cancer cells. Sci. Rep. 7 43927

    Article  Google Scholar 

  14. Dos Santos SN, Sheldon H, Pereira JX, Paluch C, Bridges EM, El-Cheikh MC, Harris AL and Bernardes ES 2017 Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation. Oncotarget 8 49484–49501

    Article  Google Scholar 

  15. Gomes TL, Fernandes RC, Vieira LL, Schincaglia RM, Mota JF, Nóbrega MS, Pichard C and Pimentel GD 2019 Low vitamin D at ICU admission is associated with cancer, infections, acute respiratory insufficiency, and liver failure. Nutrition 60 235–240

    CAS  Article  Google Scholar 

  16. Granato T, Manganaro L, Petri L, Porpora MG, Viggiani V, Angeloni A and Anastasi E 2016 Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer. Tumour Biol. 37 2177–2181

    CAS  Article  Google Scholar 

  17. Huang CX, Zhao JN, Zou WH, Li JJ, Wang PC, Liu CH and Wang YB 2014 Reduction of galectin-3 expression reduces pituitary tumor cell progression. Genet. Mol. Res. 13 6892–6898

    CAS  Article  Google Scholar 

  18. Kuittinen T, Rovio P, Staff S, Luukkaala T, Kallioniemi A, Grénman S, Laurila M and Mäenpää J 2017 Paclitaxel, Carboplatin and 1,25-D3 inhibit proliferation of endometrial cancer cells in vitro. Anticancer Res. 37 6575–6581

    CAS  PubMed  Google Scholar 

  19. Li D, Wang X, Wu JL, Quan WQ, Ma L, Yang F, Wu KY and Wan HY 2013 Tumor-produced versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and vitamin D3 signaling to promote ovarian cancer progression in vitro. PLoS ONE 8 e56616

    CAS  Article  Google Scholar 

  20. Lin YC, Lee HH, Tseng SC, Lin KD, Tseng LP, Lee JF, Lee YH and Chen BH 2019 Quantitation of serum 25(OH) D2 and 25(OH) D3 concentrations by liquid chromatography tandem mass spectrometry in patients with diabetes mellitus. J. Food Drug Anal. 27 510–517

    CAS  Article  Google Scholar 

  21. Liu L, Hu Z, Zhang H, Hou Y, Zhang Z, Zhou G and Li B 2016 Vitamin D postpones the progression of epithelial ovarian cancer induced by 7, 12-dimethylbenz [a] anthracene both in vitro and in vivo. Onco Targets Ther. 9 2365–2375

  22. May T, Comeau R, Sun P, Kotsopoulos J, Narod SA, Rosen B and Ghatage P 2017 A comparison of survival outcomes in advanced serous ovarian cancer patients treated with primary debulking surgery versus neoadjuvant chemotherapy. Int. J. Gynecol. Cancer 27 668–674

    Article  Google Scholar 

  23. Nakajima K, Heilbrun LK, Hogan V, Smith D, Heath E and Raz A 2016 Positive associations between galectin-3 and PSA levels in prostate cancer patients: a prospective clinical study-I. Oncotarget 7 82266–82272

    Article  Google Scholar 

  24. Posa F, Di Benedetto A, Colaianni G, Cavalcanti-Adam EA, Brunetti G, Porro C, Trotta T, Grano M, et al. 2016 Vitamin D effects on osteoblastic differentiation of mesenchymal stem cells from dental tissues. Stem Cells Int. 2016 9150819

    Article  Google Scholar 

  25. Rago T, Scutari M, Loiacono V, Santini F, Tonacchera M, Torregrossa L, Giannini R, Borrelli N, et al. 2017 Low elasticity of thyroid nodules on ultrasound elastography is correlated with malignancy, degree of fibrosis, and high expression of Galectin-3 and Fibronectin-1. Thyroid 27 103–110

    CAS  Article  Google Scholar 

  26. Schulz H, Schmoeckel E, Kuhn C, Hofmann S, Mayr D, Mahner S and Jeschke U 2017 Galectins-1, -3, and -7 are prognostic markers for survival of ovarian cancer patients. Int. J. Mol. Sci. 18 1230

  27. Stiasny A, Freier CP, Kuhn C, Schulze S, Mayr D, Alexiou C, Janko C, Wiest I, et al. 2017 The involvement of E6, p53, p16, MDM2 and Gal-3 in the clinical outcome of patients with cervical cancer. Oncol. Lett. 14 4467–4476

    Article  Google Scholar 

  28. Takenaka Y, Fukumori T, Yoshii T, Oka N, Inohara H, Kim HR, Bresalier RS and Raz A 2004 Nuclear export of phosphorylated galectin-3 regulates its antiapoptotic activity in response to chemotherapeutic drugs. Mol. Cell Biol. 24 4395–4406

    CAS  Article  Google Scholar 

  29. Topcu TO, Kavgaci H, Gunaldi M, Kocoglu H, Akyol M, Mentese A, Yaman SO, Orem A, et al. 2018 The clinical importance of serum galectin-3 levels in breast cancer patients with and without metastasis. J. Cancer Res. Ther. 14 S583–S586

    CAS  Article  Google Scholar 

  30. Vaughan-Shaw PG, Zgaga L, Theodoratou E, Blackmur JP and Dunlop MG 2019 Whether vitamin D supplementation protects against colorectal cancer risk remains an open question. Eur. J. Cancer 115 1–3

    CAS  Article  Google Scholar 

  31. Wang HS and Wang LH 2015 The expression and significance of Gal-3 and MUC1 in colorectal cancer and colon cancer. Onco. Targets Ther. 8 1893–1898

    CAS  Article  Google Scholar 

  32. Zhang J, Yang S, Xu B, Wang T, Zheng Y, Liu F, Ren F, Jiang J, et al. 2019 p62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor. Cell Prolif. 52 e12585

    Article  Google Scholar 

  33. Zhang L, Luo M, Yang H, Zhu S, Cheng X and Qing C 2019 Next-generation sequencing-based genomic profiling analysis reveals novel mutations for clinical diagnosis in Chinese primary epithelial ovarian cancer patients. J. Ovarian Res. 12 19

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China; Contract Grant Number: 81571437. Nanjing Health Bureau Medical Science Foundation (No. YKK16203)

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Correspondence to Jingmin Zhang.

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Corresponding editor: Kundan Sengupta

Communicated by Kundan Sengupta.

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Ji, J., Cheng, X., Wang, W. et al. Vitamin D regulates cell viability, migration and proliferation by suppressing galectin-3 (Gal-3) gene in ovarian cancer cells. J Biosci 45, 69 (2020). https://doi.org/10.1007/s12038-020-00038-1

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Keywords

  • Galectin-3 (Gal-3)
  • migration
  • proliferation
  • ovarian cancer
  • viability
  • vitamin D