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Study regarding NT157 effects, a multitarget antineoplastic, in lung cancer cell models

Grant number: 20/12748-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2021
Effective date (End): December 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:João Agostinho Machado Neto
Grantee:Lívia Bassani Lins de Miranda
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Lung cancer is the most incident neoplasm in the world, with the exception of no melanoma skin cancer. In 2018 it was diagnosed in nearly 2 million people, and it was responsible for around 18,4% of the deaths among all types of cancer. Molecular mechanisms play a role in different tumor aspects, such as aggressiveness, and, although those mechanisms have already been studied, they are still not widely used as therapeutic targets. Studies regarding lung cancer showed that different pathways involved in cell proliferation and survival, IGF1R for instance, are more expressed, whereas stress induced pathways, such as MAPK pathways, have reduced expression. NT157 is a synthetic drug initially described as a IGF1R/IR1-2 and STAT3 inhibitor. Moreover, later studies indicated its effect in other pathways, including the PI3K/AKT and JNK signaling pathways and the tyrosine kinase receptor AXL. The current study aims to elucidate the NT157's effects in lung cancer cells, as well as investigate its influence in pathways already described in previous researches studying distinct cell models. Therefore, well established lung cancer cell lines will be utilized for characterization of the signaling pathways expression, as well as NT157's effects in those cells. For this study techniques such as real time PCR and Western blot analysis will be performed, additionally to cell essays to analyses cell's viability, apoptosis, migration and invasion. Our expectation is to clarify NT157's effects and possibly propose a new drug for lung cancer treatment.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LIPRERI DA SILVA, JEAN CARLOS; CARVALHO, MARIA FERNANDA LOPES; DE MIRANDA, LIVIA BASSANI LINS; DE ALMEIDA, BRUNA OLIVEIRA; LIMA, KELI; MACHADO-NETO, JOAO AGOSTINHO. NSC305787, a pharmacological ezrin inhibitor, exhibits antineoplastic activity in pancreatic cancer cells. INVESTIGATIONAL NEW DRUGS, v. N/A, p. 10-pg., . (19/23864-7, 20/12909-7, 20/12748-3)
LINS DE MIRANDA, LIVIA BASSANI; LIMA, KELI; COELHO-SILVA, JUAN LUIZ; TRAINA, FABIOLA; KOBAYASHI, SUSUMU S.; MACHADO-NETO, JOAO AGOSTINHO. NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells. SCIENTIFIC REPORTS, v. 12, n. 1, p. 11-pg., . (19/23864-7, 20/12748-3, 21/11606-3)

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