Effect of treatment with melatonin associated with paclitaxel in ovarian carcinoma cells

Author(s)

Leticia Barbosa Gaiotte

• Document type: Master's Dissertation
• Press: Botucatu. 2022-03-23.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2022-02-17
• Advisor: Luiz Gustavo de Almeida Chuffa

Abstract

Ovarian cancer (OC) is a gynecological disease with high mortality rates among women. Although most patients respond to the conventional chemotherapy [e.g., paclitaxel (PTX)], many women become resistant and the disease progresses. Melatonin exerts antioxidants, antitumor, and immunomodulatory functions in a variety of solid tumors. Therefore, this study investigated the effects of PTX combined with melatonin on the toll-like receptor (TLR) mediated inflammatory pathway, cell signaling, and survival of SKOV-3 human ovarian carcinoma cells. The flow cytometry assay showed that melatonin associated with PTX promoted a significant increase in apoptosis/necrosis rates. The cell migration was attenuated by melatonin alone, and after its association with PTX, the number of migrated and invasive cells reduced significantly. Although the combined treatment of PTX and melatonin was unable to reduce TLR2, the levels of TLR4, MyD88, TRIF, and PD-L1 were reduced following therapy combination and even melatonin alone. Furthermore, the combination therapy significantly reduced the levels of NF-kB p65, p-PI3K, p-AKT, p38, ERK 1/2, JNK, CREB, p70s6K, and STAT 5. We concluded that the combined treatment was effective in reducing OC cell viability and invasive capacity while increasing apoptosis and necrosis rates. Moreover, the combination attenuated the downstream molecules of the TLR4-mediated inflammatory pathway and cell signaling-related proteins in SKOV-3 cells, thus proving to be capable of promoting changes in the cellular response and in its malignant potential. Melatonin may improve the chemosensitivity of PTX, serving as an effective adjuvant therapy against OC. (AU)

• FAPESP's process: 20/00544-4 - Effect of treatment with melatonin associated with paclitaxel on ovarian carcinoma cells
• Grantee: Leticia Barbosa Gaiotte
• Support Opportunities: Scholarships in Brazil - Master