Pharmacological Research - Modern Chinese Medicine (Dec 2022)
A diverse treatment with the extract of Euphorbia fischeriana Steud. and Ziziphus jujuba Mill. for breast cancer nude mice of MCF-7 (ER+) cells or MDA-MB-453 (ER-) cells via modulation of the PI3k/Akt signalling pathway
Abstract
Background: The extract of Euphorbia fischeriana Steud. and Ziziphus jujuba Mill. (ESZM) is a formula composed of Euphorbia fischeriana Steud. (E. fischeriana) and Ziziphus jujuba Mill. (Z. jujuba). Previous studies have shown that the ESZM extract has good anti-breast cancer effects in vitro. However, its in vivo therapeutic efficacy and underlying mechanism are still unclear, particularly for different subtypes of breast cancer. Our study aimed to investigate the pharmacological effects and the underlying molecular mechanism of the ESZM extract on growth inhibition and apoptosis in breast cancer nude mice of MCF-7 (ER+) cells or MDA-MB-453 (ER-) cells Methodology: In this paper, growth inhibition, cell cycle arrest and apoptosis of tumour tissues treated with the ESZM extract in ER(+) or ER(-) breast cancer xenografts were determined based on the tumour inhibition rates, using a cycle analysis kit, Annexin V-FITC/PI and Hoechst 33,342/PI staining and TEM observations, and a TUNEL test. The related gene and protein expression levels were measured using a qRT-PCR assay, Western blotting, immunohistochemistry and immunofluorescence. Serum biochemistry tests and H&E staining were performed to evaluate the toxicity of the ESZM extract. Results: The results showed that the ESZM extract could inhibit the cell growth, block the cell cycle at the G2/M phase, and induce the apoptosis of subcutaneously transplanted tumours, especially of ER(-) breast cancer transplanted tumours. Furthermore, we demonstrated that the polyjuice could down-regulate or up-regulate the expression of the Bcl-2 family factors and of PI3k/Akt pathway-related signalling molecules in vivo. The ESZM extract increased the levels of ALT, AST, Cr and BUN, and increased the hepatic and renal toxicity in cancer-bearing mice. Conclusions: these experimental results indicate that the ESZM extract has significant anti-breast cancer effects, particularly in ER(-) breast cancer xenografts, which might be implemented through the mitochondrion-dependant and the PI3k/Akt signalling pathways. The toxicity tests showed that the ESZM extract may have hepatorenal toxicity. Finally, we believe that the ESZM extract can be developed as a novel therapeutic option for the treatment of breast carcinoma.
