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Impact of Nintedanib and Anti-Angiogenic Agents on Uveal Melanoma Cell Behavior
Vera E Pawlik1, Svenja R Sonntag1, Salvatore Grisanti1
1Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
Purpose:
The purpose of this study was to investigate the direct impact of the combined angiokinase inhibitor nintedanib as well as the anti-angiogenic agents ranibizumab, bevacizumab, and aflibercept on the primary uveal melanoma (UM) cell line Mel270 and liver metastasis UM cell line OMM2.5.
Methods:
The metabolic activity, viability, and oxidative stress levels were analyzed by the Thiazolyl Blue Tetrazolium Bromide (MTT), LIVE/DEAD, and reactive oxygen species (ROS) assays. Expression of intracellular VEGF-A165 and VEGF receptor-2 was detected by immunofluorescent staining. The secretion of VEGF-A165 into the cell culture supernatants was evaluated by VEGF-A165 ELISA.
Results:
Nintedanib, at a concentration of 1 µg/mL, resulted in a median reduction of metabolic activity (for Mel270 of approximately 38% and for OMM2.5 of 46% compared to the untreated control) without exerting toxicity in either cell line, whereas the other 3 substances did not result in any changes (which also means that none of the 4 substances led to an increased cell death). Moreover, nintedanib (1 µg/mL) induced oxidative stress in the Mel270 by approximately 1.2 to 1.5-fold compared to the untreated control, but not the OMM2.5 cells.
Conclusions:
Nintedanib could suppress the growth of UM cells in a concentration-dependent manner. The metastatic UM cell line OMM2.5 was not sensitive to the pro-oxidant activity of nintedanib. This study was the first to investigate nintedanib in the context of UM. We propose further investigation of this substance to elucidate its effects on this tumor entity with the hope of identifying advantageous therapeutic options for future adjuvant tumor therapies.
Insights
Nintedanib reduced uveal melanoma (UM) cell metabolic activity without toxicity, unlike other anti-angiogenic drugs. Further research is recommended for nintedanib as a potential therapy for UM.
Area of Science:
- Oncology
- Pharmacology
Background:
- Uveal melanoma (UM) is a rare primary eye cancer.
- Anti-angiogenic therapies are crucial in cancer treatment.
Purpose of the Study:
- To investigate the direct impact of nintedanib, an angiokinase inhibitor, and anti-angiogenic agents (ranibizumab, bevacizumab, aflibercept) on UM cell lines.
- To evaluate the efficacy of these agents on primary (Mel270) and metastatic (OMM2.5) UM cells.
Main Methods:
- Cell viability, metabolic activity, and oxidative stress were assessed using MTT, LIVE/DEAD, and ROS assays.
- Expression of VEGF-A165 and its receptor-2 was analyzed via immunofluorescence.
- VEGF-A165 secretion was quantified using ELISA.
Main Results:
- Nintedanib (1 µg/mL) significantly reduced metabolic activity in Mel270 (38%) and OMM2.5 (46%) cells without inducing toxicity.
- Other tested anti-angiogenic agents did not alter metabolic activity or viability.
- Nintedanib induced oxidative stress in Mel270 cells but not OMM2.5 cells.
Conclusions:
- Nintedanib demonstrated a concentration-dependent suppression of UM cell growth.
- The metastatic OMM2.5 cell line showed insensitivity to nintedanib's pro-oxidant effects.
- This study highlights nintedanib as a potential therapeutic agent for UM, warranting further investigation for adjuvant therapies.
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