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JTC-801 Suppresses Melanoma Cells Growth through the PI3K‑Akt‑mTOR Signaling Pathways
1School of Medicine, Shandong University, Jinan, Shandong, P.R. China - Department of Dermatology, Shandong Provincial Third Hospital, Jinan, Shandong, P.R. China.
Abstract:
Melanoma is considered as one of the most potentially fatal and aggressive malignancies. Due to the limited efficacy or drug resistance of the current targeted therapies of melanoma, developing new therapeutic drugs against new targets to effectively control tumor growth is greatly needed. In this study, the effect of JTC-801, a selective small-molecule antagonist of nociceptin receptor and analgesic agent, on a melanoma cell line, M14, has been studied. We demonstrate herein that JTC-801 could efficiently suppress the proliferation, migration and invasion capacity of the M14 melanoma cells, and induced a strong apoptosis. Importantly, our results provide the underlying molecular mechanism of these effects. JTC-801 cells regulate M14 cells by inhibiting the PI3K-Akt‑mTOR pathway. These results suggest that JTC-801 should be further studied in preclinical modes to establish whether it represents a potential small anticancer candidate drug against melanoma.
Insights
JTC-801, a novel drug, effectively inhibits melanoma cell growth, migration, and invasion by targeting the PI3K-Akt-mTOR pathway. Further research is warranted to explore its potential as an anticancer therapeutic for melanoma.
Area of Science:
- Oncology
- Pharmacology
Background:
- Melanoma is an aggressive cancer with limited treatment options.
- Current targeted therapies for melanoma often face efficacy limitations or drug resistance.
- There is a critical need for novel therapeutic agents targeting new pathways to control melanoma growth.
Purpose of the Study:
- To investigate the anti-melanoma effects of JTC-801, a selective nociceptin receptor antagonist.
- To elucidate the molecular mechanisms underlying JTC-801's action on melanoma cells.
Main Methods:
- Utilized the M14 melanoma cell line for in vitro studies.
- Assessed the impact of JTC-801 on cell proliferation, migration, invasion, and apoptosis.
- Investigated the modulation of the PI3K-Akt-mTOR signaling pathway by JTC-801.
Main Results:
- JTC-801 significantly suppressed proliferation, migration, and invasion of M14 melanoma cells.
- JTC-801 treatment induced substantial apoptosis in melanoma cells.
- The observed effects were mediated by the inhibition of the PI3K-Akt-mTOR pathway.
Conclusions:
- JTC-801 demonstrates potent anti-melanoma activity in vitro.
- Inhibition of the PI3K-Akt-mTOR pathway is a key mechanism for JTC-801's anti-cancer effects.
- JTC-801 warrants further preclinical investigation as a potential melanoma therapeutic agent.
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