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Updated: Feb 22, 2026
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Preclinical study of CC223 as a potential anti-ovarian cancer agent
Zhenzhen Jin1, Huanfu Niu1, Xuenan Wang1
1Center for Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining, China.
Abstract:
Aberrant activation of mTOR contributes to ovarian cancer progression. CC223 is a novel and potent mTOR kinase inhibitor. The current study tested its activity against human ovarian cancer cells. We showed that CC223, at nM concentrations, inhibited survival and proliferation of established/primary human ovarian cancer cells. Further, significant apoptosis activation was observed in CC223-treated ovarian cancer cells. CC223 disrupted assembly of mTOR complex 1 (mTORC1) and mTORC2 in SKOV3 cells. Meanwhile, activation of mTORC1 and mTORC2 was almost completely blocked by CC223. Intriguingly, restoring mTOR activation by introduction of a constitutively-active Akt1 only partially inhibited CC223-induced cytotoxicity in SKOV3 cells. Further studies showed that CC223 inhibited sphingosine kinase 1 (SphK1) activity and induced reactive oxygen species (ROS) production in SKOV3 cells. At last, oral administration of CC223 potently inhibited SKOV3 xenografted tumor growth in nude mice. The results of this study imply that CC223 could be further studied as a potential anti-ovarian cancer agent.
Insights
The novel mTOR inhibitor CC223 effectively combats ovarian cancer by blocking cell survival, proliferation, and inducing apoptosis. It also demonstrated significant tumor growth inhibition in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Aberrant activation of the mechanistic target of rapamycin (mTOR) pathway is a key driver in ovarian cancer progression.
- Targeting mTOR represents a promising therapeutic strategy for ovarian cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of CC223, a novel mTOR kinase inhibitor, against human ovarian cancer cells.
- To elucidate the molecular mechanisms underlying CC223's anti-cancer activity in ovarian cancer.
Main Methods:
- In vitro testing of CC223 on human ovarian cancer cell lines (established and primary).
- Assessment of cell survival, proliferation, apoptosis, and mTORC1/mTORC2 complex assembly and activation.
- In vivo studies using SKOV3 xenograft models in nude mice to evaluate tumor growth inhibition.
Main Results:
- CC223 exhibited potent inhibition of ovarian cancer cell survival and proliferation at nanomolar concentrations.
- CC223 induced significant apoptosis and blocked mTORC1 and mTORC2 activation in ovarian cancer cells.
- CC223 inhibited sphingosine kinase 1 (SphK1) activity, increased reactive oxygen species (ROS) production, and suppressed tumor growth in vivo.
Conclusions:
- CC223 demonstrates significant anti-ovarian cancer activity through multiple molecular pathways, including mTOR inhibition.
- CC223 shows potential as a therapeutic agent for ovarian cancer and warrants further clinical investigation.
