Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell

Author(s)

Buss, Julieti Huch ^[1] ; Begnini, Karine Rech ^[1] ; Bruinsmann, Franciele Aline ^[2] ; Ceolin, Taise ^[2] ; Sonego, Mariana Souza ^{[1, 3]} ; Pohlmann, Adriana Raffin ^{[4, 2]} ; Guterres, Silvia Staniscuaski ^[2] ; Collares, Tiago ^{[1, 3]} ; Seixas, Fabiana Kommling ^{[1, 3]}

Affiliation

^[1] Univ Fed Pelotas, Mol & Cellular Oncol Res Grp, Lab Canc Biotechnol, Technol Dev Ctr, Pelotas - Brazil

^[2] Univ Fed Rio Grande do Sul, Pharmaceut Sci, Porto Alegre, RS - Brazil

^[3] Univ Fed Pelotas, Technol Dev Ctr, Postgrad Program Biotechnol, Pelotas - Brazil

^[4] Univ Fed Rio Grande do Sul, Inst Chem, Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 9, APR 9 2019.
• Web of Science Citations: 1

Abstract

Transitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to advanced stage tumors. Lapatinib is an important alternative to treat tumors that presents this phenotype due to its ability to inhibit tyrosine kinase residues associated with HER1 and HER2 receptors. This study evaluated the cytotoxicity induced by LAP-loaded nanocapsules (NC-LAP) compared to LAP in HER-positive bladder cancer cell. The cytotoxicity induced by NC-LAP was evaluated through flow cytometry, clonogenic assay and RT-PCR. NC-LAP at 5 mu M reduced the cell viability and was able to induce G0/G1 cell cycle arrest with up-regulation of p21. Moreover, NC-LAP treatment presented significantly higher apoptotic rates than untreated cells and cells incubated with drug-unloaded nanocapsules (NC) and an increase in Bax/Bcl-2 ratio was observed in T24 cell line. Furthermore, clonogenic assay demonstrated that NC-LAP treatment eliminated almost all cells with clonogenic capacity. In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants