mohammadreza roshanazadeh

Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.

Various members of the Tripartite-motif protein family contribute to different types of cancer, although the role of these factors in breast cancer is unclear. TRIM14 and TRIM29 have been reported to be overexpressed and play oncogenic roles in specific cancers.

A total of 40 pairs of tumor tissues and adjacent normal tissues of breast cancer patients were obtained. Relative gene expression of TRIM14 and TRIM29 were determined through quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)  using specific primers.

TRIM14 and TRIM29 were both overexpressed in breast tumor samples. The expression of TRIM14 was associated with tumor size, stage, and invasiveness. Nonetheless, no association was found between TRIM14 and the grade of the tumor. Also, TRIM29 gene expression was positively correlated with tumor size, stage, grade, and invasiveness. No correlation was found between the expression of TRIM14 and TRIM29.

Based on our results, we propose TRIM14 and TRIM29 as potential tumor markers in breast cancer.

Cancer cell metastasis is facilitated by matrix-metalloproteinases through degradation of extracellular matrix (ECM) proteins and is a major cause of mortality. One of the most common remedies for cancer is chemotherapy, which has many side effects. Therefore, it seems necessary to find a way to reduce the side effects of these drugs while maintaining their anticancer effects. Quercetin (que) is a natural substance that has been reported to have anticancer activities.

This study aims at evaluating the effect of que in combination with doxorubicin (dox) on the migration of the MDA-MB231 breast cancer cell line.

The effects of que and dox on cell viability in 24h and 48 h was assessed by MTT assay. Also, the effects of the same drugs on the cancer cells migration were evaluated, using the wound healing assay. Lastly, the effects of que and dox were assessed on the expression of MMP-2 and MMP-9 genes.

The combination of 50 µM of que with 32 nM of dox was selected by CI comparison. The viability and migration of cancer cells and the gelatinases genes expression were decreased after treatment with individual drugs. The migration and the expression of MMP-2 and MMP-9 genes after treatment with the combination of que and dox was significantly reduced compared to the treatment with que and dox alone.

Que inhibits the viability and migration of MDA-MB-231 cancer cells and synergistically enhances the effects of dox on the survival and migration of these cells. Hence, we propose this drug combination as a path for further research on breast cancer therapy.

Breast cancer (BC) cells’ ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues. Hence, researchers have focused on finding a way to reduce the dose of chemotherapeutic drugs. Quercetin, a natural polyphenolic compound, has inhibitory effects on proliferation and migration of tumor cells. This study evaluated the effect of the combination of Quercetin and 5-fluorouracil  on migration of the MDA-MB-231 breast cancer cell line. The effect of Quercetin, 5-fluorouracil , and their combination on MDA-MB-231 breast cancer cell proliferation was investigated through MTT assay. Inhibition of tumor cell migration was examined by wound healing assay. Finally, the effect of treatments on gene expression of MMP-2 and MMP-9 was evaluated by quantitative real-time PCR. The IC50 values for Quercetin and 5-fluorouracil  after 48 hr treatment were 295 μM and 525 μM, respectively. The combination index (CI) for Quercetin and 5-fluorouracil  was <1, indicating synergy between them. The combination of Quercetin plus 5-fluorouracil  resulted in a significant reduction in migration rate and MMP-2 and MMP-9 gene expressions of MDA-MB-231 cancer cells compared with the individual application of 5-FU. Quercetin enhances the suppressory effect of 5-fluorouracil  on migration of BC cells. The combination of Quercetin and 5-fluorouracil  can be an attractive field for future studies.