The concurrent effects of azurin and Mammaglobin-A genes in inhibition of breast cancer progression and immune system stimulation in cancerous BALB/c mice

Abstract

In the present study, the simultaneous application of azurin gene of P. aeruginosa and MAM-A antigen on the induction of immune responses against breast cancer tumors was investigated in BALB/c mice. The pBudCE4.1-azurin-MAM-A recombinant vector was generated and prepared at a large scale. This recombinant vector alone or combined with chitosan nanoparticles was infused into the hip muscle of animals. Animals were divided into the "prevention" and "therapy" categories. The animals of prevention category were first, immunized by a recombinant vector and then exposed to chemical cancer inducers; while the animals in the therapy category were first treated with chemical compounds and then infused by a recombinant plasmid. The tumor tissues, infusion sites, and blood specimens were collected and examined by serological, molecular, and histological tests. The breast tumor incidence in the infused animals by recombinant plasmid alone or combined with nanoparticles (in both prevention and therapy categories) compared with infused mice by empty pBudCE4.1 vector was significantly decreased (p < 0.05). These results were supported by histological studies using H&E staining. The ELISA and q-real-time PCR techniques showed the range of IFN-γ, IL-12, IL-4, and IL-17A cytokines in the infused mice by recombinant vector alone or combined with nanoparticles compared to the healthy mice and infused animals by intact pBudCE4.1 were significantly increased (p < 0.05). Accordingly, the expression of the tumor markers CEA, Krt20, and Muc1 were significantly decreased in treated mice either by the sole recombinant vector or combined with nanoparticles (p < 0.05). These findings indicated that pBudCE4.1-azurin-MAM-A recombinant vector plays an essential role against the formation and expansion of breast tumors in the animal model. In addition, this recombinant vector is safe and has the proper ability to stimulate the immune system. In addition, the chitosan nanoparticle represents a promising adjuvant for DNA vaccine delivery, which improves the immune system stimulation and boosts the vaccine performance.

Enhancement of anticancer effect of azurin using polymeric nanoparticles

“…High toxicity is critical in producing anticancer drugs; although toxicity results in this research were satisfying, it takes much effort to put these valuable results into use at clinical levels. Encapsulating Az with CS can protect it from the attack of the immune system and can help to pass through main drug-resistant mechanisms [1,45,46] ; in addition, it helps Az to remain in the targeted areas longer than free protein and extends drug releasing time. One of the problems we face in common cancer treatments is that in treatments like chemotherapy, there is no border in attacking healthy and cancerous cells, but by using nanocarriers, we can reduce the harmful attacks on healthy cells.…”

Mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) expression in different breast cancer subtypes and their clinical significance

“…Mammaglobin is a well-known specific marker for breast cancer, and the high expression of mammaglobin is associated with tumour stage, 9 histological grading, 3,6 lymph node metastasis, 3,19 and endocrine state. 5,6 In this study, we found mammaglobin expression to be significantly associated with lymph node status, histopathological grade, and Ki-67 expression, despite its low sensitivity.…”

“…Mammaglobin is a well-known specific marker for breast cancer, and the high expression of mammaglobin is associated with tumour stage, 9 histological grading, 3,6 lymph node metastasis, 3,19 and endocrine state. 5,6 In this study, we found mammaglobin expression to be significantly associated with lymph node status, histopathological grade, and Ki-67 expression, despite its low sensitivity. These findings agree with those reported by previous studies, in which mammaglobin overexpression was found to be correlated with lymph node metastasis and was identified as a potential protein metastasis marker in breast cancer patients.…”

“…3,4 Mammaglobin overexpression is associated with breast cancer occurrence and metastasis. 5,6 The protein GATA3 has also been found to participate in oestradiol regulation via a transcriptional circuitry that links it to oestrogen receptor α (ERα). 7,8 Abnormal GATA3 non-expression may cause ERα to not accumulate and induce excessive accumulation of factors critical in epithelial-tomesenchymal transition and metastasis; this promotes tumour cell metastasis and induces aggressive breast cancer phenotypes and poor prognosis.…”

Utilization of Cheese Whey for Production of Azurin by Pseudomonas aeruginosa

“…Azurin has attracted much attention in the last two decades, because it preferentially enters into many human cancer cells and induce apoptosis [8,[13][14][15]. This protein and its derived peptide p28 have anticancer activity that has been confirmed in mouse-based tumor models and various cancer cells [16,17].…”