OncoTargets and Therapy (Nov 2020)
Simultaneous Treatment with Soluble Forms of GAS1 and PTEN Reduces Invasiveness and Induces Death of Pancreatic Cancer Cells
Abstract
Lizbeth Daniel-García,1 Paula Vergara,1 Araceli Navarrete,1 Rosa O González,2 Jose Segovia1 1Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City 07300, Mexico; 2Departamento de Matemáticas, Universidad Autónoma Metropolitana-Iztapala, Mexico City 09340, MéxicoCorrespondence: Jose SegoviaDepartamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN # 2508, Mexico City 07300, MéxicoTel +52 55 5747-3958Fax +52 55 5061-3754Email [email protected]: Pancreatic carcinoma cells exhibit a pronounced tendency to invade along and through intra and extrapancreatic nerves, even during the early stages of the disease, a phenomenon called perineural invasion (PNI). Thus, we sought to determine the effects of the simultaneous expression of soluble forms of GAS1 and PTEN (tGAS1 and PTEN-L) inhibiting tumor growth and invasiveness.Materials and Methods: We employed a lentiviral system to simultaneously express tGAS1 and PTEN-L; in order to determine the effects of the treatments, cell viability and apoptosis as well as the expression of the transgenes by ELISA and intracellular signaling as ascertained by the activation of AKT and ERK1/2 were measured; cell invasiveness was determined using a Boyden chamber assay; and the effects of the treatment were measured in vivo in a mouse model.Results: In the present work, we show that the combined treatment with tGAS1 and PTEN-L inhibits the growth of pancreatic cancer cells, by reducing the activities of both AKT and ERK 1/2, decreases cell invasiveness, and restrains tumor growth in a mouse model.Conclusion: The combined administration of tGAS1 and PTEN-L could be a valuable adjunct therapy for the treatment of pancreatic cancer.Keywords: growth arrest specific 1, PTEN-L, pancreatic cancer, perineural invasion, artemin, GFRα 3
