Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

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Mynampati Bharani; Enghelberg Moises; V.Chalam Kakarla

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Journal: MEDICAL HYPOTHESIS, DISCOVERY AND INNOVATION OPHTHALMOLOGY Year:2020 | Volume:9 | Issue:1 Page(s): 7-14

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Title

Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

Author(s)

Mynampati Bharani | Enghelberg Moises | V.Chalam Kakarla | Issue Writer Certificate

Keywords

Pazopanib

In vitro

Age Related Macular Degeneration

Vacular Endothelial Growth Factor

Choroidal Vascular Endothelial Cell

Bevacizumab

Ranibizumab

Aflibercept

Abstract

Exudative Age Related Macular Degeneration (AMD) is related to active choroidal neovascularization (CNV) and formation of disciform scars. Vascular endothelial growth factor (VEGF) mediated Choroidal Vascular Endothelial Cell (CVECs) proliferation is characteristic of CNV. Intravitreal injections of Bevacizumab, Ranibizumab and Aflibercept (anti-VEGF monoclonal antibodies) are used to treat exudative AMD. Pazopanib, a tyrosine kinase inhibitor, inhibits neovascularization through blockade of intracellular tyrosine kinase VEGF receptor and platelet-derived growth factor receptor. In this In vitro investigation, we evaluated the inhibitory consequences of escalating doses of Pazopanib on proliferation of VEGF-enriched CVECs to establish a safe dosage range. VEGF (50 ng/mL) enriched CVECs were treated with escalating doses of Pazopanib (10, 50, 100 and 250 μ M). Cell proliferation rates (WST-1 assay), cell viability (trypan blue exclusion assay), and reactive oxygen species (ROS) levels were measured at 48 hours (h), 72h and 1 week. Intracellular caspase 3 levels and morphological changes were recorded. VEGF enriched CVECs showed a significant decrease in cell proliferation rates after one week of treatment with increasing doses of Pazopanib (10, 50, 100 and 250 μ M) treatment i. e. 87. 8%, 43. 0%, 38. 1% and 9. 3% compared to controls (p<0. 001). Similarly, trypan blue exclusion assay revealed a decrease in cell viability as 81. 8%, 81. 0%, 53. 4% and 8. 7%, respectively (p<0. 05). Further, Pazopanib actively inhibited proliferation of VEGF-enriched CVECs, with 1. 32, 1. 92, 1. 92 and 4. 1-fold increase (p<0. 01) in intracellular caspase 3 levels. VEGF-enriched CVECs treated with escalating doses of Pazopanib decreased cell viability and increased caspase 3 levels in a time and dose dependent manner...

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APA: Copy

Mynampati, Bharani, Enghelberg, Moises, & V.Chalam, Kakarla. (2020). Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis. MEDICAL HYPOTHESIS, DISCOVERY AND INNOVATION OPHTHALMOLOGY, 9(1), 7-14. SID. https://sid.ir/paper/782147/en

Vancouver: Copy

Mynampati Bharani, Enghelberg Moises, V.Chalam Kakarla. Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis. MEDICAL HYPOTHESIS, DISCOVERY AND INNOVATION OPHTHALMOLOGY[Internet]. 2020;9(1):7-14. Available from: https://sid.ir/paper/782147/en

IEEE: Copy

Bharani Mynampati, Moises Enghelberg, and Kakarla V.Chalam, “Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis,” MEDICAL HYPOTHESIS, DISCOVERY AND INNOVATION OPHTHALMOLOGY, vol. 9, no. 1, pp. 7–14, 2020, [Online]. Available: https://sid.ir/paper/782147/en

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