Zoledronic acid-loaded lipidic nanoparticles enhance apoptosis and attenuate invasiveness by inhibiting epithelial to mesenchymal transition (EMT) in HepG 2 cancer cells

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2021-12, Vol.394 (12), p.2429
• Main Authors: Sabzichi, Mehdi, Oladpour, Omolbanin, Mohammadian, Jamal, Rashidi, Mohsen, Hosseinzadeh, Mahla, Mardomi, Alireza, Ramezani, Bahman, Ghorbani, Marjan, Ramezani, Fatemeh
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis - drug effects; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell Movement - drug effects; Epithelial-Mesenchymal Transition - drug effects; Hep G2 Cells; Humans; Inhibitory Concentration 50; Liposomes; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Nanoparticles; Neoplasm Invasiveness; Paclitaxel - administration & dosage; Zoledronic Acid - administration & dosage
• ISSN: 1432-1912
• DOI: 10.1007/s00210-021-02164-5

The aim of this study was to evaluate the potential of zoledronic acid (ZOL)-loaded lipidic nanoparticles (ZOL-NLCs) in enhancing the efficiency of paclitaxel (Pac) in the context of cytotoxicity, apoptosis, and invasiveness of HepG hepatocellular carcinoma cells. ZOL-NLCs were characterized in terms of zeta potential, particle size, and scanning electron microscope (SEM) as well as cell internalization. To measure the anti-proliferative effects of ZOL-NLCs, annexin-V/PI and MTT assays were employed. Real-time PCR and western blot analysis were performed to identify the molecular mechanisms underlying the apoptosis in response to the studied conditions. Furthermore, the transwell migration assay was applied to clarify the role of applied formulations on the invasiveness of HepG cells. Our results demonstrated that the optimized ZOL had an average particle size of 105 ± 6 nm with a nearly narrow size distribution. The IC values for ZOL and ZOL-NLCs were 90 ± 3.1 and 54.6 ± 2.4 µM, respectively. The population of apoptotic cells was increased from 17 ± 2% to 27 ± 4% (p