A scorpion peptide reported to exhibit both analgesic and antitumor activity in animal models may present as an alternative therapeutic agent for breast cancer. We aimed to investigate the effect of Buthus martensii Karsch antitumor-analgesic peptide (BmK AGAP) on breast cancer cell stemness and epithelial-mesenchymal transition (EMT). We treated MCF-7 and MDA-MB-231 cells with different concentrations of rBmK AGAP and observed that rBmK AGAP inhibited cancer cell stemness, epithelial-mesenchymal transition (EMT), migration, and invasion. Analysis by qPCR, ELISA, western blot, immunofluorescence staining, sphere formation, colony assay, transwell migration, and invasion assays demonstrated rBmK AGAP treatment decreased the expressions of Oct4, Sox2, N-cadherin, Snail, and increased the expression of E-cadherin. rBmK AGAP inhibited breast cancer cell stemness, EMT, migration, and invasion by down-regulating PTX3 through NF-κB and Wnt/β-catenin signaling Pathway in vitro and in vivo. Xenograft tumor model confirmed inhibition of tumor growth, stem-like features, and EMT by rBmK AGAP. Thus, rBmK AGAP is a potential therapeutic agent against breast cancer and related pain.

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Background: The present study aimed to investigate the possibility of using intravoxel incoherent motion (IVIM) diffusion magnetic resonance imaging (MRI) to quantitatively assess the early therapeutic effect of the analgesic–antitumor peptide BmK AGAP on breast cancer and also evaluate the medical value of a reduced distribution of four b -values. Methods: IVIM diffusion MRI using 10 b -values and 4 b -values (0–1,000 s/mm 2 ) was performed at five different time points on BALB/c mice bearing xenograft breast tumors treated with BmK AGAP. Variability in Dslow , Dfast , PF , and ADC derived from the set of 10 b -values and 4 b -values was assessed to evaluate the antitumor effect of BmK AGAP on breast tumor. Results: The data showed that PF values significantly decreased in rBmK AGAP-treated mice on day 12 ( P = 0.044). PF displayed the greatest AUC but with a poor medical value (AUC = 0.65). The data showed no significant difference between IVIM measurements acquired from the two sets of b -values at different time points except in the PF on the day 3. The within-subject coefficients of variation were relatively higher in Dfast and PF . However, except for a case noticed on day 0 in PF measurements, the results indicated no statistically significant difference at various time points in the rBmK AGAP-treated or the untreated group ( P < 0.05). Conclusion: IVIM showed poor medical value in the early evaluation of the antiproliferative effect of rBmK AGAP in breast cancer, suggesting sensitivity in PF . A reduced distribution of four b-values may provide remarkable measurements but with a potential loss of accuracy in the perfusion-related parameter PF .

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