Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer.

Breast cancer is one of the most common tumors in women. Current data indicate that the overexpression of some microRNAs (miRNAs) is associated with breast cancer, in relation to stage, tumor size and potential for metastasis. Some studies have reported that miRNAs have critical roles in cellular processes implicated in breast cancer cell growth, migration and metastasis by targeting the PI3K/AKT oncogenic signaling pathway. Therefore, identifying novel regulatory miRNAs for this oncogenic pathway and discovery of their related target genes may represent a promising therapeutic approach for breast cancer therapy. This review highlights the recent findings about the potential role of PI3K/AKT signaling regulatory miRNAs in breast cancer tumorigenesis.

Association of a genetic variant in ATP-binding cassette sub-family B member 1 gene with poor prognosis in patients with squamous cell carcinoma of the esophagus.

Esophageal cancer is a common cause of death from cancer in men and the eighth most prevalent cancer globally. The morbidity and mortality rates are four times higher in men than in women. Genetic factors are among the susceptibility factors for squamous cell carcinoma of the esophagus. The rs2032582 polymorphism is a triallelic missense variant of the ABCB1 gene, that has been reported to be associated with several cancers. Here we have explored the association of the ABCB1 rs2032582 polymorphism with esophageal squamous cell carcinoma (ESCC) for the first time in a total of 251 subjects, with and without ESCC. Data from patient's record were obtained from the Mashhad University of Medical Sciences, and were used to recruit ESCC patients into the study. A total of 89 ESCC patients and 162 healthy controls were included. DNAs were extracted and genotyped using a TaqMan real-time PCR-based method. Caplan Meier method was applied to analyze patients overall survival, and progression-free survival and log-rank were used in order to compare the results. Logistic regression was used to calculate the association between risk of ESCC and different genotypes. Our data showed that patients with ESCC had a higher frequency of a T/A (TT/TA/AA) genotype for rs2032592 than individuals with GG-genotype. There were no associations between BMI and genotypic frequencies. Furthermore patients with TT/TA/AA genotypes had a poorer disease-free survival (P = 0.016) in comparison with GG genotype. We found a significant association of the ABCB1 rs2032582 polymorphism with prognosis, although further studies in a larger and multicenter setting are needed to value these findings. © 2019 IUBMB Life, 71(9):1252-1258, 2019.

Synergistic effects of Ferula gummosa and radiotherapy on induction of cytotoxicity in HeLa cell line.

OBJECTIVE: Cervical cancer is the second most common type of cancer among women, worldwide; and for treatment of this type of cancer radiotherapy is commonly used. Ferula gummosa Boiss ("Barije" in Persian, from the family Apiaceae), (F. gummosa), is an extremely precious medicinal plant which naturally grows throughout the Mediterranean and Central Asia and is a native plant in Iran. The present study examined the cytotoxic effects of F. gummosa in terms of induction of apoptosis and radiosensitivity in HeLa cells. MATERIALS AND METHODS: In order to determine F. gummosa cytotoxicity in HeLa cells, the cells were incubated with different concentrations of the plant resin (0-1000 µg/ml) for 24, 48 and 72 hr. Cytotoxicity was determined by MTT assay. The role of apoptosis in F. gummosa cytotoxicity was investigated using flow cytometry following propidium iodide (PI) staining of DNA. For radiosensitivity assessment, F. gummosa-treated cells were exposed to 2 Gy γ-rays, and cytotoxicity was determined in irradiated and non-irradiated (control) groups by MTT and the synergism factor was calculated. RESULTS: F. gummosa decreased cell viability in HeLa cells in a concentration- and time-dependent manner. Flow cytometry analysis indicated that apoptosis is involved in F. gummosa-induced cytotoxicity. Co-administration of F. gummosa and radiotherapy, showed that this plant at non-toxic low doses, could result in almost 5-fold increment in sensitization of cells towards radiation-induced toxicity. CONCLUSION: The concurrent use of F. gummosa and radiation increases radiosensitivity and cell death. Therefore, F. gummosa can be considered as a potential radiosensitizer agent against cervical cancer.

Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer.

OBJECTIVES: P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA-mediated P-gp downregulation. MATERIALS AND METHODS: NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamine™ (OFA) in vitro and in vivo. RESULTS: Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. CONCLUSION: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy.

Effect of Rosmarinus officinalis L. aerial parts extract on morphine withdrawal syndrome in mice.

The effect the aqueous and ethanol extracts of Rosmarinus officinalis L. aerial parts on morphine withdrawal syndrome was investigated in mice. The aqueous and ethanol extracts induced a significant antinociceptive activity in the writhing test. This activity was inhibited by naloxone pretreatment. Dependence was induced using subcutaneous injections of morphine daily for 3 days. On day 4, morphine was injected 2 h prior to the intraperitoneal injection of naloxone. The number of jumps during the 30 min period after naloxone injection was considered as a measure of the withdrawal syndrome. The results indicated that the aqueous (1.68 g/kg and 2.4 g/kg, i.p.) and ethanol (0.96 g/kg, i.p.) extracts reduced the number of jumps. Phytochemical study indicated that only the aqueous extract of R. officinalis has an alkaloid component. It is concluded that the aqueous and ethanol extracts of R. officinalis aerial parts could diminish morphine withdrawal syndrome.