2. Academic Validation
  3. Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway

Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway

  • J Cancer. 2026 Jan 1;17(2):245-256. doi: 10.7150/jca.113511.
Sisi Kuang 1 2,  Weifeng Feng 3,  Siqi He 4,  Wei Meng 5,  ChunYan Yang 6,  Yingxia Ning 5 1
Affiliations

Affiliations

  • 1 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
  • 2 Department of Reproductive Medicine, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • 3 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
  • 4 Faculty of Arts and Science,University of Toronto, Toronto, Ontario, Canada.
  • 5 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 6 Department of Gynaecology and Obstetrics, The second people's hospital of Huaihua City (Tumor hospital of Huaihua City), Huaihua, Hunan, China.
PMID: 41584043 DOI: 10.7150/jca.113511
Abstract

6RK73 is a novel drug designed to target UCHL1 Deubiquitinase. Preliminary studies have indicated its anti-cancer activity in breast Cancer and renal cell carcinoma. However, its potential anti-cancer effects in Other malignancies, including ovarian Cancer, remain unclear. In this study, we first determined the IC50 values of 6RK73 in ovarian Cancer cell lines OVCAR3 and SKOV3, which were 10.62 μM and 12.90 μM, respectively. Subsequently, we found that 6RK73 effectively inhibited cell proliferation and arrested cell cycle progression in ovarian Cancer cells in vitro. Furthermore, 6RK73 suppressed the formation of subcutaneous ovarian Cancer tumors in nude mice. Mechanistically, 6RK73 significantly inhibited the Akt1/Sp1/c-Myc signaling pathway, which not only disrupted the interaction between Sp1 and c-Myc but also reduced Sp1 deubiquitination, thereby downregulating c-Myc protein expression. Interestingly, the anti-tumor effects of 6RK73 in ovarian Cancer were independent of UCHL1 inhibition. Finally, Akt1 overexpression reversed the 6RK73-mediated suppression of cell proliferation by reactivating the Akt1/Sp1/c-Myc signaling pathway. These findings suggest that 6RK73 is a promising anti-cancer agent that exerts its effects by inactivating Akt1/Sp1/c-Myc signaling in ovarian Cancer.

Keywords

6RK73; AKT1; Sp1; UCHL1; c-Myc; ovarian cancer.

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