The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (−16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC₅₀ values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher—although not statistically significant—tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.

Cell fusion is a physiological cellular process essential for fertilization, viral entry, muscle differentiation and placental development, among others. In this review, we will highlight the different cancer cell-cell fusions and the advantages obtained by these fusions. We will specially focus on the acquisition of metastatic features by cancer cells after fusion with bone marrow-derived cells. The mechanism by which cancer cells fuse with other cells has been poorly studied thus far, but the presence in several cancer cells of syncytin, a trophoblastic fusogen, leads us to a cancer cell fusion mechanism similar to the one used by the trophoblasts. The mechanism by which cancer cells perform the cell fusion could be an interesting target for cancer therapy.

The syncytiotrophoblast (STB) is a multinuclear layer forming the outer surface of the fetal part of the placenta deriving from villous cytotrophoblastic cell (vCTB) fusion and differentiation. This syncytialization process is characterized by morphological and biochemical alterations of the trophoblast, which probably require removal of pre-existing structures and proteins to maintain cell homeostasis and survival. Interestingly, autophagy, which allows degradation and recycling of cellular components, was shown to be activated in syncytiotrophoblast. Here we examined the involvement of endoplasmic reticulum stress (ERS) response in autophagy activation during vCTB syncytialization. We first demonstrated the activation of ERS response and autophagy during the time course of trophoblastic cell fusion and differentiation. Alteration of autophagy activation in vCTB by chemical treatments or Beclin-1 expression modulation leads to a decrease in trophoblastic syncytialization. Furthermore, ERS response inhibition by chemical treatment or siRNA strategy leads to a default in syncytialization, associated with alteration of autophagy markers and cell survival. From these data, we suggest that ERS response, by fine regulation of autophagy activation, may serve as an adaptive mechanism to promote cell survival during trophoblastic syncytialization.

Polyploid giant cancer cells (PGCCs) have been observed in epithelial ovarian tumors and have the ability to survive to antimitotic drugs. Their appearance can result from paclitaxel treatment or hypoxia, two conditions known to induce unfolded protein response (UPR) activation. PGCCs produced under hypoxia may be formed by cell fusion and can contribute by bursting and budding to the generation of cancer stem-like cells which have a more aggressive phenotype than the parental cells. Despite the fact that PGCCs may contribute to tumor maintenance and recurrence, they were poorly studied. Here, we confirmed that PGCCs could derive, at least in part, from cell fusion. We also observed that PGCCs nuclei were able to fuse. The resulting cells were able to proliferate by mitosis and were more invasive than the parental cancer cells. Using two different ovarian cancer cell lines (COV318 and SKOV3), we showed that UPR activation with chemical inducers increased cell fusion and PGCCs appearance. Down-regulation of the UPR-associated protein PERK expression partially reversed the UPR-induced PGCCs formation, suggesting that the PERK arm of the UPR is involved in ovarian PGCCs onset.