Page 64 - SDIR5 Abstract book 21 12 2021.
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POSTER PRESENTATIONS



               P24




                 MiR-93-5p expression in response to the systemic, targeted, and combinational therapy for
                            metastatic colorectal cancer and therapy resistance: in vitro analysis

                                                    1
                                   Jovana Despotović , Zoran Krivokapić 2,3,4 , Aleksandra Nikolić 1
                       1  Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
                                  2  Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade, Serbia
                                      3  School of Medicine, University of Belgrade, Belgrade, Serbia
                                       4  Serbian Academy of Sciences and Arts, Belgrade, Serbia

               Background: Addition of a targeted agent bevacizumab to the systemic chemotherapy (5-fluorouracil (5-
               FU)  combined  with  oxaliplatin)  improves  the  survival  of  metastatic  colorectal  cancer  (mCRC)  patients.
               However, half of them do not respond to therapy, so a challenge remains to identify treatment response
               biomarkers.  The  expression  of  microRNAs  has  been  associated  with  the  therapeutic  response  and
               resistance  in  CRC.  The  aim  of  this  study  was  to  analyze  the  miR-93-5p  expression  in  response  to  the
               systemic,  targeted,  and  combinational  therapy  for  mCRC  and  its  potential  role  in  therapy  resistance.
               Material  and  Methods:  Human  metastatic  colon  adenocarcinoma  SW620  cells  and  colonic  epithelial
               progenitor HCEC-1CT cells were treated with FOX (21.4 μM 5-FU + 85 μM oxaliplatin) and/or 25, 85 and
               250 µg/mL bevacizumab for 72 h. Cell response was evaluated through cell viability using MTT assay, while
               miR-93-5p  expression  was  analyzed  by  quantitative  reverse  transcription  polymerase  chain  reaction.
               Expression of hsa-miR-93-5p was also analyzed in 5-FU-resistant SW620 cells. Results: FOX and FOX/250
               µg/mL bevacizumab treatments significantly reduced viability of SW620 and HCEC-1CT cells. Increasing
               concentrations of bevacizumab alone or in combination with FOX reduced the viability of HCEC-1CT cells.
               FOX and FOX/250 µg/mL bevacizumab combination significantly decreased miR-93-5p expression in HCEC-
               1CT cells, but not in SW620 cells. Expression of miR-93-5p was similar in SW620 cells compared to the 5-
               FU-resistant SW620 cells. Conclusion: Combination of targeted and systemic treatment for mCRC affects
               SW620 viability, but not miR-93-5p expression. MiR-93-5p was not associated with 5-FU resistance. Thus,
               miR-93-5p does not have a role in therapy response or resistance in mCRC.
               Keywords: metastatic colorectal cancer, chemotherapy, bevacizumab, hsa-miR-93-5p
               Acknowledgement: This study was funded by the Serbian Academy of Sciences and Arts [F-69].










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