Prostaglandin F 2α synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F 2α -dependent and F 2α -independent mechanism.
| Autor: | Wang YJ; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Xie XL; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Liu HQ; Liver Unit, University of Calgary, Calgary T1W0K6, Canada., Tian H; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Jiang XY; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Zhang JN; Department of Gastroenterology, The Affiliated Hospital of Hebei Engineering University, Handan 056000, Hebei Province, China., Chen SX; Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Liu T; Department of Gastroenterology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Wang SL; Department of Gastroenterology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Zhou X; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Jin XX; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China., Liu SM; Department of Gastroenterology, Hebei Youfu Hospital, Shijiazhuang 050000, Hebei Province, China., Jiang HQ; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. jianghuiqing1959@sina.com. |
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| Jazyk: | angličtina |
| Zdroj: | World journal of gastroenterology [World J Gastroenterol] 2023 Oct 21; Vol. 29 (39), pp. 5452-5470. |
| DOI: | 10.3748/wjg.v29.i39.5452 |
| Abstrakt: | Background: Oxaliplatin (Oxa) is the first-line chemotherapy drug for colorectal cancer (CRC), and Oxa resistance is crucial for treatment failure. Prostaglandin F Aim: To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC. Methods: The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels. Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance (HCT116-OxR and HCT8-OxR) and their parental cell lines (HCT116 and HCT8) to assess its influence on cell proliferation, chemoresistance, apoptosis, and DNA damage. For determination of the underlying mechanisms, CRC cells were examined for platinum-DNA adducts and reactive oxygen species (ROS) levels in the presence of a PGFS inhibitor or its products. Results: Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues. Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dose-dependent manner. Furthermore, overexpression of PGFS in parental CRC cells significantly attenuated Oxa-induced proliferative suppression, apoptosis, and DNA damage. In contrast, knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells (HCT116-OxR and HCT8-OxR) accentuated the effect of Oxa treatment in vitro and in vivo . The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa. Treatment with the PGFS-catalyzed product PGF Conclusion: PGFS promotes resistance to Oxa in CRC via both PGF Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest in our study. (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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