Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines

Abstract

Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).

Herb Extracellular Vesicle-Chitosan-PEGylated Graphene Oxide Conjugate Delivers Estrogen Receptor α Targeting siRNA to Breast Cancer Cells

“…For all EVs and NEV conjugates, post 24 h of incubation with MCF7 cells, the percentage of cell survival was appreciable and showed an insignificant difference, supporting the excellent biocompatibility of the EVs and the NEV conjugates. In the case of antiproliferative activity, Figure A–C shows the migration distance at 0 and 24 h, imaged after the transfection with EV and their respective complexes. ,, In particular, we observed significant morphological changes and antiproliferative activity for cells transfected with MEV-CS-GP conjugates (Figure S5). The proliferative characteristics are connected to the subsequent metastasis process, in which cells spread to nearby tissues and invade to form metastasis.…”

“…In the case of antiproliferative activity, Figure 4A− C shows the migration distance at 0 and 24 h, imaged after the transfection with EV and their respective complexes. 42,51,52 In particular, we observed significant morphological changes and antiproliferative activity for cells transfected with MEV-CS-GP conjugates (Figure S5). The proliferative characteristics are connected to the subsequent metastasis process, in which cells spread to nearby tissues and invade to form metastasis.…”

Glioblastoma U-87 cell electrotaxis is hindered by doxycycline with a concomitant reduction in the matrix metallopeptidase-9 expression

“…Moreover, although the motility of the U87 cells was enhanced by doxycycline, the MMP-9 level was not increased in the Dox-CTL group compared with the CTL group. Previous reports have indicated that the suppression of the MMP-9 activity inhibited the wound healing migration ( in vitro scratch assay) of human lung cancer cells [ 68 ], human MCF-7 breast cancer cells [ 69 ], and human hepatocellular carcinoma cells [ 70 ], and suppressed the migration of MDA-MB-231 human breast cancer cells in an in vitro transwell migration assay [ 71 ]. These results agree with ours, as the downregulation of MMP-9 reduced the migration potential of U87 cells.…”

Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

“…In the study by Gao et al [ 160 ], migration was reduced in the cancer cells after the introduction of E3Ab, and the protein expression of MMP-9 was reduced by E3Ab. Previous studies have demonstrated that MMP-9 plays an important role in the migration of cancer cells such as MDA-MB-231 [ 163 , 164 ]. Interestingly, in a previous study, Gao et al [ 165 ] showed that the blockage of Nav1.5 channel in MDA-MB-231 reflected a decrease in MMP-9.…”