Gemcitabine and Synthesized Silver Nanoparticles Impact on Chemically Induced Hepatocellular Carcinoma in Male Rats

Abstract

Purpose Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used for the treatment of many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used in the treatment of many diseases such as infectious diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficency of the co-treatment of gemcitabine and silver nanoparticles in hepatocellular carcinoma treatment. Methods AgNPs characterization has been done using UV- visible spectroscopy, XRD, TEM, and EDX. Firstly, the MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. Then after HCC development, rats received (10µg/g b.wt.) of AgNPs three times a week for four weeks and/or GEM (5mg/kg b.wt.) twice weekly for four weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. Results The co-treatment of GEM and AgNPs showed upregulation of apoptosis by increasing Bax and caspase 9 while diminishing Bcl2 and SMAD4, amelioration of cytochrome P450 m-RNA relative expression. In addition, the results proved the cooperative effect of GEM and AgNPs in the deactivation of miR21. Conclusion The impact of AgNPs as an adjuvant treatment with GEM was recognized. The interaction between AgNPs and Gem can diminish some of the drawbacks of using GEM alone and elevate its efficiency in HCC treatment via enhancing intrinsic and extrinsic apoptotic pathways.