Article Data

  • Views 1743
  • Dowloads 103

Original Research

Open Access

Umbilical cord-derived mesenchymal stem cells efficiently induced apoptosis of endometrial carcinoma cells

  • J. Zheng1,†
  • P. Liu2,†
  • C. Li1
  • L. Cheng1
  • Y. Xu1
  • F. Guo1
  • M. Xiong1
  • T. Song1
  • Y. Li1
  • F. Yan1
  • H. Xu1
  • B. Chen1,*,
  • J. Zhang1

1Department of Gynecology and Obstetrics, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi, China

2Department of Otolaryngological, Tangdu, The Fourth Military Medical University, Xi'an, Shanxi, China

DOI: 10.12892/ejgo4919.2019 Vol.40,Issue 5,October 2019 pp.839-845

Accepted: 30 October 2018

Published: 10 October 2019

*Corresponding Author(s): B. Chen E-mail: chenbiliang1962@sina.com

† These authors contributed equally.

Abstract

Purpose of Investigation: To investigate the mechanism of apoptosis of AN3CN cells, an endometrial cancer (EC) cell line, induced by human umbilical cord mesenchymal stem cells (hUCMSCs). Materials and Methods: UC-MSCs and AN3CN cells were co-cultured and CCK-8 cell proliferation assay was used to assess cell proliferation. Results: By co-culture with hUCMSCs, the proliferation of AN3CN cells was significantly inhibited (p < 0.001) and the cell cycle of AN3CN cells was arrested in the G2 phase. Furthermore, this study indicated that changes in the PI3K/Erk/JNK/Bcl-2/DR5 signal pathway-related genes promoted apoptosis of AN3CN cells. Conclusion: This finding not only helps us understand the molecular mechanism of hUCMSCs inhibiting tumor growth and promoting apoptosis, but also provides us a strong rationale to further investigate hUCMSCs as a potential treatment of EC.

Keywords

Apoptosis; AN3CN cells; Human umbilical cord mesenchymal stem cells; PI3K/Erk/JNK/Bcl-2/DR5

Cite and Share

J. Zheng,P. Liu,C. Li,L. Cheng,Y. Xu,F. Guo,M. Xiong,T. Song,Y. Li,F. Yan,H. Xu,B. Chen,J. Zhang. Umbilical cord-derived mesenchymal stem cells efficiently induced apoptosis of endometrial carcinoma cells. European Journal of Gynaecological Oncology. 2019. 40(5);839-845.

References

[1] Chen W., Zheng R., Baade P.D., Zhang S., Zeng H., Bray F. et al.: “Cancer statistics in China, 2015”. CA Cancer J. Clin., 2016, 66, 115.

[2] Siegel R.L., Miller K.D., Jemal A.: “Cancer statistics, 2016”. CA. Cancer J. Clin., 2016, 66, 7.

[3] Rhee K.J., Lee J.I., Eom Y.W.: “Mesenchymal Stem Cell-Mediated Effects of Tumor Support or Suppression”. Int. J. Mol. Sci., 2015, 16, 30015.

[4] Bexell D., Scheding S., Bengzon J.: “Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectors”. Mol. Ther., 2010, 18, 1067.

[5] Bajetto A., Pattarozzi A., Corsaro A., Barbieri F., Daga A., Bosio A. et al.: “Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors”. Front. Cell. Neurosci., 2017, 11, 312.

[6] Studeny M., Marini F.C., Dembinski J.L., Zompetta C., CabreiraHansen M., Bekele B.N. et al.: “Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents”. J. Natl. Cancer Inst., 2004, 96, 1593.

[7] Kidd S., Spaeth E., Dembinski J.L., Dietrich M., Watson K., Klopp A. et al.: “Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging”. Stem Cells, 2009, 27, 2614.

[8] La Rocca G., Anzalone R., Corrao S., Magno F., Loria T., Lo Iacono M. et al.: “Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers”. Histochem. Cell. Biol., 2009, 131, 267.

[9] Si Y.L., Zhao Y.L., Hao H.J., Fu X.B., Han W.D.: “MSCs: Biological characteristics, clinical applications and their outstanding concerns”. Ageing. Res. Rev., 2011, 10, 93.

[10] Baraniak P.R., McDevitt T.C.: “Stem cell paracrine actions and tissue regeneration”. Regen. Med., 2010, 5, 121.

[11] Ciavarella S., Caselli A., Tamma A.V., Savonarola A., Loverro G., Paganelli R. et al.: “A peculiar molecular profile of umbilical cordmesenchymal stromal cells drives their inhibitory effects on multiple myeloma cell growth and tumor progression”. Stem Cells Dev., 2015, 24, 1457.

[12] Bieback K., Kern S., Kluter H., Eichler H.: “Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood”. Stem Cells, 2004, 22, 625.

[13] Wang Y., Gao C., Zhang Y., Gao J., Teng F., Tian W. et al.: “Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways”. Gynecol. Oncol., 2016, 143, 168.

[14] Siegel R., Desantis C., Jemal A.: “Colorectal cancer statistics, 2014”. CA Cancer J. Clin., 2014, 64, 104.

[15] Husseinzadeh N., Husseinzadeh H.D.: “mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: a critical review”. Gynecol. Oncol., 2014, 133, 375.

[16] Sadeghi N., Gerber D.E.: “Targeting the PI3K pathway for cancer therapy”. Future Med. Chem., 2012, 4, 1153.

[17] Bauer T.M., Patel M.R., Infante J.R.: “Targeting PI3 kinase in cancer”. Pharmacol. Ther., 2015, 146, 53.

[18] de Melo A.C., Paulino E., Garces A.H.: “A Review of mTOR Pathway Inhibitors in Gynecologic Cancer”. Oxid. Med. Cell. Longev., 2017, 2017, 4809751.

[19] Amran D., Sanchez Y., Fernandez C., Ramos A.M., de Blas E., Breard J. et al.: “Arsenic trioxide sensitizes promonocytic leukemia cells to TNFalpha-induced apoptosis via p38-MAPK-regulated activation of both receptor-mediated and mitochondrial pathways”. Biochim. Biophys. Acta, 2007, 1773, 1653.

[20] Kim J.Y., Lee S.G., Chung J.Y., Kim Y.J., Park J.E., Koh H. et al.: “Ellipticine induces apoptosis in human endometrial cancer cells: the potential involvement of reactive oxygen species and mitogenactivated protein kinases”. Toxicology, 2011, 289, 91.

[21] Yamauchi J., Itoh H., Shinoura H., Miyamoto Y., Hirasawa A., Kaziro Y. et al.: “Involvement of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in alpha1B-adrenergic receptor/Galphaq-induced inhibition of cell proliferation”. Biochem. Biophys. Res. Commun., 2001, 281, 1019.

[22] Kang Y.H., Lee S.J.: “The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells”. J. Cell. Physiol., 2008, 217, 23.

[23] Jeon E.S., Lee M.J., Sung S.M., Kim J.H.: “Sphingosylphosphorylcholine induces apoptosis of endothelial cells through reactive oxygen species-mediated activation of ERK”. J. Cell. Biochem., 2007, 100, 1536.

[24] Shin G.C., Kim C., Lee J.M., Cho W.S., Lee S.G., Jeong M. et al.: “Apigenin-induced apoptosis is mediated by reactive oxygen species and activation of ERK1/2 in rheumatoid fibroblast-like synoviocytes”. Chem. Biol. Interact., 2009, 182, 29.

[25] Murphy L.O., Blenis J.: “MAPK signal specificity: the right place at the right time”. Trends. Biochem. Sci., 2006, 31, 268-275.

[26] Yang H., Yang R., Liu H., Ren Z., Wang C., Li D. et al.: “Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha increased apoptosis of human endometrial cancer HEC-1A cells”. Onco. Targets. Ther., 2016, 9, 5329.

[27] Nikolic I., Kastratovic T., Zelen I., Zivanovic A., Arsenijevic S., Mitrovic M.: “Cytosolic pro-apoptotic SPIKE induces mitochondrial apoptosis in cancer”. Biochem. Biophys. Res. Commun., 2010, 395, 225.

[28] Janke C., Bulinski J.C.: “Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions”. Nat. Rev. Mol. Cell. Biol., 2011, 12, 773.

[29] Magiera M.M., Janke C.: “Post-translational modifications of tubulin”. Curr. Biol., 2014, 24, R351.

[30] Park I.Y., Chowdhury P., Tripathi D.N., Powell R.T., Dere R., Terzo E.A. et al.: “Methylated alpha-tubulin antibodies recognize a new microtubule modification on mitotic microtubules”. MAbs., 2016, 8, 1590.

[31] Tanaka T., Bai T., Yukawa K.: “Suppressed protein expression of the death-associated protein kinase enhances 5-fluorouracil-sensitivity but not etoposide-sensitivity in human endometrial adenocarcinoma cells”. Oncol. Rep., 2010, 24, 1401.

[32] Wang S., El-Deiry W.S.: “TRAIL and apoptosis induction by TNF- family death receptors”. Oncogene, 2003, 22, 8628.

Submission Turnaround Time

Top