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Published on: September 15, 2023
Verteporfin inhibits papillary thyroid cancer cells proliferation and cell cycle through ERK1/2 signaling pathway
Tian Liao1, Wen-Jun Wei1, Duo Wen1
1Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Abstract:
Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC.
Insights
Verteporfin, an FDA-approved drug, shows promise in treating papillary thyroid cancer (PTC) by inhibiting cancer cell growth and tumor development. This study highlights its potential anticancer effects via the ERK1/2 signaling pathway.
Area of Science:
- Oncology
- Pharmacology
Background:
- Verteporfin, an FDA-approved photosensitizer, exhibits anticancer properties in various tumors.
- Its efficacy against papillary thyroid cancer (PTC) has not been previously established.
Purpose of the Study:
- To investigate the effects of verteporfin on PTC cell proliferation, apoptosis, cell cycle, and tumor growth.
- To explore the underlying molecular mechanisms, including the ERK1/2 signaling pathway.
Main Methods:
- Pre-clinical pilot study using PTC cell lines.
- Assessment of cell proliferation, apoptosis, and cell cycle progression.
- Xenograft mouse model to evaluate tumor growth suppression.
- Analysis of ERK1/2 and MEK phosphorylation following MEK inhibitor (U0126) treatment.
Main Results:
- Verteporfin significantly attenuated PTC cell proliferation.
- It induced cell cycle arrest in the G2/S phase and promoted apoptosis in PTC cells.
- Verteporfin treatment dramatically suppressed tumor growth in a xenograft mouse model.
- Inhibition of MEK and ERK1/2 phosphorylation was observed in verteporfin-treated PTC cells.
Conclusions:
- Verteporfin demonstrates significant inhibitory effects on PTC cell proliferation and tumor growth.
- These effects are partially mediated through the ERK1/2 signaling pathway.
- The findings support further investigation of verteporfin as a potential therapeutic agent for PTC.
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