Abstract
Cancer, as a group, represents the most important cause of death worldwide. Unfortunately, the available therapeutic approaches of cancer including surgery, chemotherapy, radiotherapy, and immunotherapy are unsatisfactory and represent a great challenge as many patients have cancer recurrence and severe side effects. Methotrexate (MTX) is a well-established (antineoplastic or cytotoxic) chemotherapy and immunosuppressant drug used to treat different types of cancer, but its usage requires high doses causing severe side effects. Therefore, we need a novel drug with high antitumor efficacy in addition to safety. The aim of this study was the evaluation of the antitumor efficacy of zinc oxide nanoparticle (ZnO-NPs) and sorafenib alone or in combination on solid Ehrlich carcinoma (SEC) in mice. Sixty adult female Swiss-albino mice were divided equally into 6 groups as follows: control, SEC, MTX, ZnO-NPs, sorafenib, and ZnO-NPs+sorafenib; all treatments continued for 4 weeks. ZnO-NPs were characterized by TEM, zeta potential, and SEM mapping. Data showed that ZnO-NPs synergized with sorafenib as a combination therapy to execute more effective and safer anticancer activity compared to monotherapy as showed by a significant reduction (P < 0.001) in tumor weight, tumor cell viability, and cancer tissue glutathione amount as well as by significant increase (P < 0.001) in tumor growth inhibition rate, DNA fragmentation, reactive oxygen species generation, the release of cytochrome c, and expression of the apoptotic gene caspase-3 in the tumor tissues with minimal changes in the liver, renal, and hematological parameters. Therefore, we suggest that ZnO-NPs might be a safe candidate in combination with sorafenib as a more potent anticancer. The safety of this combined treatment may allow its use in clinical trials.
Highlights
Each year, tens of millions of people are diagnosed with cancer around the world
In the present study, we aimed to evaluate the anticarcinogenic potency of sorafenib and ZnONPs alone and in combination against solid Ehrlich carcinoma compared with FDA-approved chemotherapeutic agent MTX
We evaluated the cytotoxic activity of sorafenib and ZnO-NPs alone and in combination against solid Ehrlich carcinoma compared with FDA-approved chemotherapeutic agent MTX
Summary
Tens of millions of people are diagnosed with cancer around the world. As concerns mortality, cancer is considered the second cause of death throughout the world and will soon become the first cause of death in many parts of the globe Chemotherapy is one of the most common and effective treatments for cancer which kills tumor cells using genotoxicity. MTX is a chemotherapeutic agent that was firstly used in the treatment of solid cancers by (Pierce and Dixon, 1958). It is used in the treatment of various types of tumors and autoimmune diseases [8] due to its ability to hinder cell proliferation and synthesis of nucleotide and proteins by suppression of dihydrofolate reductase of folate metabolic pathway that plays a key role in nucleotide biosynthesis pathway [9]. Previous studies proposed that coassembly of hydroxycamptothecin and MTX followed by surface covering through acidity-responsive polyethylene glycol might be a promising strategy for synergistically enhancing chemotherapy efficiency with minimized side effect synergistic therapeutic function [11]
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