Temozolomide alleviates breast carcinoma via the inhibition of EGFR/ERK/ MMP-1 pathway with induction of apoptotic events

替莫唑胺通过抑制 EGFR/ERK/MMP-1 通路并诱导细胞凋亡来缓解乳腺癌

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作者:Weijun Zhu, Fengjun Zhang, Maoyun Wang, Shuai Meng, Fang Ren

Conclusions

The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.

Methods

In-vitro anticancer activity has been conducted on MCF7 cells, and mammary carcinoma has been induced in Wistar rats by introduction of 7, 12-Dimethylbenz(a)anthracene (DMBA), which was sustained for 24 weeks. Histopathology, immunohistochemistry, cell proliferation study and apoptosis assay via TUNEL method was conducted to evaluate an antineoplastic activity of temozolomide in rat breast tissue.

Purpose

To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.

Results

IC50 value of temozolomide in MCF7 cell has been obtained as 103 μM, which demonstrated an initiation of apoptosis. The temozolomide treatment facilitated cell cycle arrest in G2/M and S phase dose dependently. The treatment with temozolomide suggested decrease of the hyperplastic abrasions and renovation of the typical histological features of mammary tissue. Moreover, temozolomide therapy caused the downregulation of epidermal growth factor receptor, extracellular signal-regulated kinase, and metalloproteinase-1 expression and upstream of p53 and caspase-3 proliferation to indicate an initiation of apoptotic events. Conclusions: The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.

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