P-MAPA and Interleukin-12 Reduce Cell Migration/Invasion and Attenuate the Toll-Like Receptor-Mediated Inflammatory Response in Ovarian Cancer SKOV-3 Cells: A Preliminary Study

Author(s):Show less -

Lupi, Luiz Antonio ^[1] ; Delella, Flavia Karina ^[2] ; Cucielo, Maira Smaniotto ^[1] ; Romagnoli, Graziela Gorete ^[3] ; Kaneno, Ramon ^[3] ; Nunes, Iseu da Silva ^[4] ; Domeniconi, Raquel Fantin ^[1] ; Martinez, Marcelo ^[5] ; Martinez, Francisco Eduardo ^[1] ; Favaro, Wagner Josa ^[6] ; de Almeida Chuffa, Luiz Gustavo ^[1]

Affiliation

^[1] UNESP Sao Paulo State Univ, Inst Biosci, Dept Anat, BR-18618689 Botucatu, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Inst Biosci, Dept Morphol, BR-18618689 Botucatu, SP - Brazil

^[3] UNESP Sao Paulo State Univ, Inst Biosci, Dept Microbiol & Immunol, BR-18618689 Botucatu, SP - Brazil

^[4] Farmabrasilis R&D Div, BR-13279020 Campinas, SP - Brazil

^[5] Univ Fed Sao Carlos, Dept Morphol & Pathol, BR-13565905 Sao Paulo - Brazil

^[6] Univ Estadual Campinas, Dept Struct & Funct Biol, UNICAMP, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Molecules; v. 25, n. 1 JAN 2020.
• Web of Science Citations: 0

Abstract

Immunotherapies have emerged as promising complementary treatments for ovarian cancer (OC), but its effective and direct role on OC cells is unclear. This study examined the combinatory effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) on cell migration/invasion, apoptosis, toll-like receptor (TLR)-mediated inflammation, and cytokine/chemokine profile in human OC cell line SKOV-3. P-MAPA and IL-12 showed cancer cell toxicity under low doses after 48 h. Although apoptosis/necrosis and the cell cycle were unchanged by the treatments, P-MAPA enhanced the sensitivity to paclitaxel (PTX) and P-MAPA associated with IL-12 significantly reduced the migratory potential and invasion capacity of SKOV-3 cells. P-MAPA therapy reduced TLR2 immunostaining and the myeloid differentiation factor 88 (MyD88), but not the TLR4 levels. Moreover, the combination of P-MAPA with IL-12 attenuated the levels of MyD88, interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB p65). The IL-12 levels were increased and P-MAPA stimulated the secretion of cytokines IL-3, IL-9, IL-10, and chemokines MDC/CCL22 and, regulated on activation, normal T cells expressed and secreted (RANTES)/CCL5. Conversely, combination therapy reduced the levels of IL-3, IL-9, IL-10, MDC/CCL22, and RANTES/CCL5. Collectively, P-MAPA and IL-12 reduce cell dynamics and effectively target the TLR-related downstream molecules, eliciting a protective effect against chemoresistance. P-MAPA also stimulates the secretion of anti-inflammatory molecules, possibly having an immune response in the OC microenvironment. (AU)

• FAPESP's process: 16/03993-9 - Effect of P-MAPA immunomodulator associated to interleukin-12 on Ovarian Cancer: in vitro and in vivo approaches involving the inflammatory process and immune system
• Grantee: Luiz Gustavo de Almeida Chuffa
• Support type: Regular Research Grants
• FAPESP's process: 19/00906-6 - Melatonin and the MT1 and MT2 receptors: effects on apoptosis, cell proliferation and migratory potential of the ovarian carcinoma cells (SKOV-3 cell line)
• Grantee: Luiz Gustavo de Almeida Chuffa
• Support type: Regular Research Grants