Open AccessGANT61 elevates chemosensitivity to cisplatin through regulating the Hedgehog, AMPK and cAMP pathways in ovarian cancer
Author(s) -
Pengfeng Zhu,
Li Wang,
Pengju Xu,
QingQing Tan,
Yi Wang,
Guannan Feng,
Lei Yuan
Publication year - 2022
Publication title -
future medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.708
H-Index - 69
eISSN - 1756-8927
pISSN - 1756-8919
DOI - 10.4155/fmc-2021-0310
Subject(s) - cisplatin , ampk , hedgehog signaling pathway , hedgehog , cancer research , ovarian cancer , chemistry , pharmacology , biology , medicine , signal transduction , chemotherapy , cancer , microbiology and biotechnology , phosphorylation , protein kinase a
Background: This study aimed to explore the effect of GANT61 on ovarian cancer (OC) chemosensitivity. Materials & methods: 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. Results: 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. Conclusion: GANT61 enforces OC chemosensitivity to cisplatin by regulating the Hedgehog, AMPK and cAMP pathways.