title: In vitro and in vivo activity of miR-92a-Locked Nucleic Acid (LNA)-Inhibitor against endometrial cancer.
abstract: BACKGROUND
  Endometrial cancer is the most common cancer of the female reproductive tract. Based on our previous studies we speculated that miR-92a exhibited pro-oncogenic properties in endometrial cancer, and therefore its inhibition could be used as a therapeutic measure in this disease. Therefore in the present study we aimed to investigate both in vitro and in vivo if inhibition of miR-92a in endometrial cancer would limit cancer cells proliferation.
  
  
  METHODS
  miR-92a expression was evaluated in four endometrial cancer cell lines using qPCR. Inhibition of miR-92a activity was obtained in endometrial cancer cell lines by a transient transfection of a custom designed Locked Nucleic Acid (LNA)-Inhibitor, developed to work both in vitro and in vivo. In vitro proliferation studies were performed using xCELLigence RTCA DP system. In vivo experiment was performed in Cby.Cg-Foxn1 < nu>/cmdb mice bearing endometrial cancer xenografts, which were intraperitoneally injected with nine dosages of 25 mg/kg of miR-205-LNA-inhibitor.
  
  
  RESULTS
  qPCR revealed increased expression of miR-92a in HEC-1-B, Ishikawa and AN3CA cells. LNA-i-miR-92a inhibited endometrial cancer growth in vitro. It was also demonstrated that systemic administration of LNA-i-miR-92a was feasible and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals, however the effect was observed until 12thexperimental day and the last three dosages did not maintain the attenuating effect with the acceleration of tumor growth observed at the end and after cessation of the intraperitoneal therapy.
  
  
  CONCLUSIONS
  Taken together, these results indicate that intraperitoneal delivery of miR-92a-LNA-modified-inhibitor is feasible, devoid of significant toxicity and moderately inhibits endometrial cancer growth in vivo, and therefore warrants further studies investigating other routes of inhibitor delivery possibly in other animal models.
authors: Laboratory of Biostructure, Chair of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, 20-090, Poland. anna.torres@wp.pl.
authors: Anna
authors: A
authors: Torres
authors: Laboratory of Biostructure, Chair of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, 20-090, Poland.
authors: Joanna
authors: J
authors: Kozak
authors: Department of Clinical Pathomorphology, Medical University of Lublin, Jaczewskiego 8a, Lublin, 20-090, Poland.
authors: Agnieszka
authors: A
authors: Korolczuk
authors: Laboratory of Biostructure, Chair of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, 20-090, Poland.
authors: Paulina
authors: P
authors: Wdowiak
authors: Laboratory of Biostructure, Chair of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, 20-090, Poland.
authors: Ewa
authors: E
authors: Domańska-Glonek
authors: Chair of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, 20-090, Poland.
authors: Ryszard
authors: R
authors: Maciejewski
authors: Chair of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, Lublin, 20-090, Poland.
authors: Kamil
authors: K
authors: Torres
keywords: Endometrial cancer; In vivo; LNA-inhibitor; Mice xenograft; Proliferation; miR-92a