Evaluation of antitumor activity of nanogallium and low dose of gamma irradiation in animal model

Abstract

Chemotherapy combined with radiotherapy is approach for cancer treatment. In the present study, Gallium nanoparticles were biologically synthesized by using Lactobacillus helveticus extracellular metabolites. Gallium nanoparticles were characterized by using transmission electron microscopy (TEM) analysis, Fourier transforms infrared spectroscopy (FTIR) and Ultraviolet-visible absorption (UV/VIS), revealed that; GaNPs were of size ranging 6–20 nm. The FTIR analysis of GaNPs showed shifting in wave number of functional groups due to their involvement in GaNPs capping and synthesis. UV/VIS scan showed absorption peak of GaNPs at 265 nm. GaNPs effectively inhibited MCF-7 proliferation in vitro with IC50 of 8.0µg/ml. In vivo study, GaNPs LD50 was found to be 10 mg/kg b.w. Evaluation of GaNPs antitumor effect and/or gamma radiation in vivo, was performed using 80 female swiss albino mice. They were divided into 8 groups, each of 10 mice. Mice were inoculated intramuscular with Ehrlich ascite carcinoma cells in the right thigh to induce a solid tumor. The results revealed that solid tumor induced a significant increase in serum ALT activity, serum creatinine level, total leucocytic count, liver MDA content, liver calcium and liver iron concentrations While GSH, CYP2E1 and Na+K+ATPase showed significant decrease compared to control group.Treating Ehrlich carcinoma (EC) bearing mice with GaNPs and/or exposure to low dose of γ-radiation (0.25 Gy) significantly reduced tumor volume, ALT activity, creatinine level and TLC in mice serum and blood respectively. Moreover, biochemical studies in the liver tissue showed a significant increase in glutathione level, Na+K+ATPase activity, CYP450 (2E1) gene expression with a significant decrease in MDA content, the calcium and iron concentrations compared to EC group. Meanwhile, biochemical studies in the tumor tissue showed a significant increase in MDA content, Na+K+ATPase, complexes II and III activity with a significant reduction in GSH level, calcium, iron concentrations and CYP450 (2E1) gene expression in mitochondria upon comparison with EC group. Also DNA fragmentation pattern of tumor tissue showed intense fragmentation accompanied with different treatments compared to EC group. Results indicate a synergestic effect of combined treatment against Ehrlich solid tumor which was well confirmed with the histopathological findings in the tumor tissue of treated groups compared to EC group.