TELMISARTAN INHIBITS MELANOMA GROWTH AND METASTASIS THROUGH LRP1 SUPPRESSION
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Date
2024-03-11
Authors
Saymeh,Danah
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Publisher
An-Najah National University
Abstract
Background: Melanoma is the most common type of skin cancer worldwide, which hasa poor prognosis becauseof its high metastatic rate and aggressive nature. Wild-type p53, which has been activated in response to cellular stressors such as oncogene activity, is commonly expressed in melanoma. It has been discovered that TP53 regulates the development of tumors mediated by the multifunctional scavenger protein LRP1 (CD91), which has been connected to the advancement of melanoma.Telmisartan, an antihypertensive medication, possesses anticancer properties that effectively treat melanoma. Moreover, Mir 107 is a crucial tumor suppressor factor that can inhibit the LRP1 oncogene.
Aims: Thisstudy aims to determine the effect of angiotensin receptor blocker telmisartan on melanoma growth and metastasis to evaluate it as a potential therapy option for patients with metastatic melanoma who wish to achieve a high survival rate.
Methods:An experimental study was carried out at the An-Najah Laboratory for Cancer and Stem Cell Research in Nablus. The B16F10 melanoma cell lineswere seeded in 12 well plates and treated with indicated concentrations of telmisartan to assess cell viability and migration.This study was conducted both in vitro and in vivo using C57BL6 mice to determine telmisartan's impact on tumor growth. To study the effect of LRP1 on melanoma cell proliferation, we utilized lentivirus to overexpress LRP1 and siRNA to knock down LRP1 in B16F10 cells. We also used lentivirus to express tumor suppressor miR107. The expressions of LRP1 (OE) LRP1(KD), and miR107 were verified by qPCR.
Results:The study showed that telmisartan inhibits the proliferation and migration of B16F10 cells both in vitro and in vivo.Additionally, the research revealed thattelmisartan restores P53 by phosphorylation, which upregulates the expression of tumor suppressor miR107 and then leadsto downregulating LRP1 expression, inhibiting melanoma growth and metastasis.