PMID- 34249430 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210713 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 11 IP - 6 DP - 2021 TI - Differential molecular response of larynx cancer cell lines to combined VPA/CDDP treatment. PG - 2821-2837 AB - Successful treatment of advanced larynx squamous cell carcinoma (LSCC) remains a challenge, mainly due to limited response to chemotherapy and the phenomenon of the drug resistance. Therefore, new chemotherapeutic solutions are needed. The aim of this study was to explore benefit of combined cisplatin (CDDP) and valproic acid (VPA) therapy in patients' derived LSCC cell lines. Cell viability assay was used to establish cellular response to the drug by isobolography followed by RNA sequencing (RNAseq) analysis. Danio rerio were used for in vivo studies. Depending on the cell line, we found that the combinations of drugs resulted in synergistic or antagonistic pharmacological interaction, which was accompanied by significant changes in genes expression profiles. The presented therapeutic scheme efficiently blocked tumor growth in an in vivo model, corresponding to the in vitro performed studies. Interestingly the RK5 cell line, upon the combined treatment acquired a molecular profile typically associated with epithelial to mesenchymal transition (EMT). Hence, our studies demonstrates that patient-specific personalized therapy of larynx cancer should be considered and the combination of cisplatin and valproic acid should be explored as a potential therapeutic strategy in the treatment of larynx cancer. CI - AJCR Copyright (c) 2021. FAU - Gumbarewicz, Ewelina AU - Gumbarewicz E AD - Department of Biochemistry and Molecular Biology, Medical University of Lublin Chodzki 1 St., 20-093 Lublin, Poland. FAU - Tylzanowski, Przemko AU - Tylzanowski P AD - Department of Biochemistry and Molecular Biology, Medical University of Lublin Chodzki 1 St., 20-093 Lublin, Poland. AD - Laboratory for Developmental and Stem Cell Biology, Department of Development and Regeneration, Skeletal Biology and Engineering Research Centre, University of Leuven Leuven, Belgium. FAU - Luszczki, Jarogniew AU - Luszczki J AD - Department of Pathophysiology, Medical University Lublin, Poland. FAU - Kalafut, Joanna AU - Kalafut J AD - Department of Biochemistry and Molecular Biology, Medical University of Lublin Chodzki 1 St., 20-093 Lublin, Poland. FAU - Czerwonka, Arkadiusz AU - Czerwonka A AD - Department of Biochemistry and Molecular Biology, Medical University of Lublin Chodzki 1 St., 20-093 Lublin, Poland. FAU - Szumilo, Justyna AU - Szumilo J AD - Department of Clinical Pathomorphology, Medical University of Lublin Lublin, Poland. FAU - Wawruszak, Anna AU - Wawruszak A AD - Department of Biochemistry and Molecular Biology, Medical University of Lublin Chodzki 1 St., 20-093 Lublin, Poland. FAU - Kupisz, Krzysztof AU - Kupisz K AD - Department of Otolaryngology and Laryngeal Oncology, Medical University of Lublin Lublin, Poland. AD - Department of Otolaryngology, Center of Oncology of The Lublin Region Lublin, Poland. FAU - Polberg, Krzysztof AU - Polberg K AD - Department of Otolaryngology, MSWiA Hospital Lublin, Poland. FAU - Smok-Kalwat, Jolanta AU - Smok-Kalwat J AD - Department of Clinical Oncology, Holycross Cancer Centre Kielce, Poland. FAU - Stepulak, Andrzej AU - Stepulak A AD - Department of Biochemistry and Molecular Biology, Medical University of Lublin Chodzki 1 St., 20-093 Lublin, Poland. LA - eng PT - Journal Article DEP - 20210615 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC8263637 OTO - NOTNLM OT - Laryngeal cancer OT - cisplatin OT - gene expression OT - valproic acid COIS- None. EDAT- 2021/07/13 06:00 MHDA- 2021/07/13 06:01 PMCR- 2021/06/15 CRDT- 2021/07/12 05:53 PHST- 2020/04/17 00:00 [received] PHST- 2021/05/14 00:00 [accepted] PHST- 2021/07/12 05:53 [entrez] PHST- 2021/07/13 06:00 [pubmed] PHST- 2021/07/13 06:01 [medline] PHST- 2021/06/15 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2021 Jun 15;11(6):2821-2837. eCollection 2021.