Description

• Title:
  MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model
• Twórca:
  Bębenek, Wiktoria;
  Gajek, Arkadiusz;
  Marczak, Agnieszka;
  Malý, Jan;
  Smejkal, Jiří;
  Statkiewicz, Małgorzata;
  Rusetska, Natalia;
  Bryś, Magdalena;
  Rogalska, Aneta
• Współtwórca:
  Uniwersytet Łódzki, Administracja, Pion bezpośrednio podległy Pani Rektor, Szkoły Doktorskie, Szkoła Doktorska Nauk Ścisłych i Przyrodniczych;
  Uniwersytet Łódzki, Wydział Biologii i Ochrony Środowiska, Instytut Biofizyki, Katedra Biofizyki Medycznej;
  Uniwersytet Łódzki, Wydział Biologii i Ochrony Środowiska, Instytut Biochemii, Katedra Cytobiochemii;
  ul0246006@edu.uni.lodz.pl;
  arkadiusz.gajek@biol.uni.lodz.pl;
  agnieszka.marczak@biol.uni.lodz.pl;
  magdalena.brys@biol.uni.lodz.pl;
  aneta.rogalska@biol.uni.lodz.pl
• Opis:
  Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity. Both HCC cell lines exhibited heightened sensitivity to the combined treatment. The effect of drugs on the expression of proliferation markers in an olaparib-resistant patient-derived xenograft (PDX) model of ovarian cancer was also investigated. Ovarian tumors displayed reduced tissue growth, as reflected by a drop in proliferation marker Ki-67 levels in response to PARPi combined with CHK1i. No changes were observed in corresponding liver tissues using Ki-67 and pCHK staining, which indicates the absence of metastases and a hepatotoxic effect. Thus, our results indicate that the dual inhibition of PARP and CHK1 may prove to be a promising therapeutic approach in the treatment of primary HCC as well as OC tumors without the risk of liver metastases, especially in patients with olaparib-resistant tumor profiles.;
  This research was partly funded by the National Science Centre, Poland (Project grant number: Sonata Bis 2019/34/E/NZ7/00056).
• Dostępność obiektu:
  free access
• Prawa: http://creativecommons.org/licenses/by/4.0
• Data:
  2025.04.15;
  2025
• Typ:
  Article
• Język:
  English
• Format:
  application/pdf
• Wydawca:
  MDPI
• Relacja:
  International Journal of Molecular Sciences;;
  26
• Temat i słowa kluczowe:
  liver cancer;
  ovarian cancer;
  metastasis;
  targeted therapy;
  olaparib;
  CHK1 inhibitor;
  replication stress
• Identyfikator:
  1661-6596;
  http://hdl.handle.net/11089/55342 ;
  1422-0067;
  10.3390/ijms26020834
• Dostawca danych:
  Repozytorium Uniwersytetu Łódzkiego
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