Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research

Abstract

Background: Breast cancer is one of the most common malignancies in women, with one in 20 globally. Oncolytic viruses have recently been the first step in the biological treatment of cancer, either genetically engineered or naturally occurring. They increase specifically inside cancer cells and destroy them without damaging normal tissues or producing a host immune response against tumour cells or expressing transgenes. One of the most known members of this family is the Newcastle disease virus (NDV), a natural oncolytic virus that selectively induces apoptosis and DNA fragmentation in human cancer cells.Methods: This study performed biochemical and molecular investigations with variable doses of NDV (32, 64, 128 HAU) and liposomal doxorubicin (9 mg/kg) on mouse triple-negative mammary carcinoma cell line 4T1 and BALB/c models tumours for the first time.Results: Real-time quantitative PCR analysis in NDV-treated animal tumours showed increased expression of P21, P27 and P53 genes and decreased expression of CD34, integrin Alpha 5, VEGF and VEGF-R genes. Additional assessments in treated mouse models also showed that NDV increased ROS production, induced apoptosis, reduced tumour size and significantly improved prognosis, with no adverse effect on normal tissues. Conclusions:These findings all together might indicate that NDV in combination with chemotherapy drugs could improve prognosis in cancer patients although many more conditions should be considered.

Complications in patients with transfusion dependent thalassemia: A descriptive cross‐sectional study

“…Iron overload disrupts the body's iron homeostasis, increasing extracellular nontransferrin‐bound iron and intracellular labile iron pool. This increase in iron levels leads to the production of reactive oxygen species by the Fenton and Haber–Weiss reaction, which subsequently induces oxidative damage to vital components of the cells 11,12 . This cellular injury can cause serious complications such as heart and renal failure, immune system disorders, growth retardation, and liver disease 13,14 .…”

“…This increase in iron levels leads to the production of reactive oxygen species by the Fenton and Haber–Weiss reaction, which subsequently induces oxidative damage to vital components of the cells. 11 , 12 This cellular injury can cause serious complications such as heart and renal failure, immune system disorders, growth retardation, and liver disease. 13 , 14 In low‐resource countries, blood transfusions with concomitant administration of iron chelators, such as Deferoxamine, L1, and Deferasirox (DFX) medications, are the most common treatment for patients with major thalassemia.…”

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

“…A lentogenic strain of NDV, called LaSota, was used to determine the oncolytic nature and efficacy of this virus in combination with doxorubicin in TNBC. The in vitro results showed that this NDV strain could replicate in and cause the cytolysis of 4T1 cancer cells in a dose-dependent manner [ 159 ]. When tested in a 4T1 syngeneic mouse model, the virus was administered at various hemagglutination unit (HAU) doses from 32 to 128, with one group featuring a combination with doxorubicin at 64 HAUs.…”

Transcriptome Analysis of Natural Killer Cells in Response to Newcastle Disease Virus Infected Hepatocellular Carcinoma Cells

“…The LaSota strain of NDV can selectively bind to the membrane of human tumor cells and enter the cytoplasm via endocytosis, resulting in apoptosis and DNA fragmentation of tumor cells [ 12 ]. In NDV-treated mouse tumors, the expression levels of P21, P27, and P53 genes were increased, while the expression levels of CD34, integrin α 5, VEGF, and VEGF-R genes were decreased [ 12 ]. ROS production and apoptosis pathways were reported to be stimulated by NDV in these mouse models.…”