Department of Gynecology, The Affiliated Changzhou Matenity & Child Health Care Hospital of Nanjing Medical University, Changzhou, 213000, China.
Department of Gynecology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215000, China.
Future Med Chem. 2022 Apr;14(7):479-500. doi: 10.4155/fmc-2021-0310. Epub 2022 Mar 24.
This study aimed to explore the effect of GANT61 on ovarian cancer (OC) chemosensitivity. OC cells (Caov-3 and SKOV-3) were treated by GANT61 alone or combined with cisplatin/taxol. The mRNA sequencing was conducted, followed by rescue experiments. GANT61 reduced OC cell viability in a dose-dependent manner and enhanced chemosensitivity to cisplatin but not to taxol. In total, 545 dysregulated genes were identified after the addition of GANT61 to cisplatin-treated OC cells, which were enriched in the AMPK, Hedgehog and cAMP pathways, then further validated by western blot. Furthermore, rescue experiments observed that AMPK pathway inhibitor and cAMP pathway inhibitor attenuated GANT61's chemosensitivity to cisplatin. GANT61 enforces OC chemosensitivity to cisplatin by regulating the Hedgehog, AMPK and cAMP pathways.
本研究旨在探讨 GANT61 对卵巢癌 (OC) 化疗敏感性的影响。用 GANT61 单独或联合顺铂/紫杉醇处理 OC 细胞 (Caov-3 和 SKOV-3)。进行了 mRNA 测序，然后进行了挽救实验。GANT61 呈剂量依赖性降低 OC 细胞活力，并增强了对顺铂的化疗敏感性，但对紫杉醇没有增强作用。在加入 GANT61 处理顺铂的 OC 细胞后，总共鉴定出 545 个失调基因，这些基因富集在 AMPK、Hedgehog 和 cAMP 通路中，然后通过 Western blot 进一步验证。此外，挽救实验观察到 AMPK 通路抑制剂和 cAMP 通路抑制剂减弱了 GANT61 对顺铂的化疗敏感性。GANT61 通过调节 Hedgehog、AMPK 和 cAMP 通路来增强 OC 对顺铂的化疗敏感性。
