Selenium Induces an Anti-tumor Effect Via Inhibiting Intratumoral Angiogenesis in a Mouse Model of Transplanted Canine Mammary Tumor Cells

Abstract

Selenium (Se) has been widely reported to possess anti-tumor effects. Angiogenesis is the formation of new blood vessels and is required to supply oxygen, nutrients, and growth factors for tumor growth, progression, and metastasis. To explore whether the anti-tumor effect of Se was associated with angiogenesis in vivo, we studied the effects of sodium selenite (Sel) and methylseleninic acid (MSA) on tumors induced by canine mammary tumor cells (CMT1211) in mice; cyclophosphamide (CTX) served as a positive control. The results showed that the Se content was significantly increased in the Sel and MSA groups. Se significantly inhibited the tumor weights and volumes. Large necrotic areas and scattered and abnormal small necrotic areas were observed in the Se treatment group. Immunofluorescence double staining showed a reduction in the microvessel density (MVD) and increment in the vessel maturation index (VMI) compared with the untreated control group. As expected, the protein and mRNA levels of the angiogenesis factors angiopoietin-2 (Ang-2), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) were decreased in the Se-treated tumors by IHC, as shown by western blotting and RT-QPCR. We also found that organic Se MSA provided stronger inhibition of tumor growth compared with inorganic sodium selenite (Sel). Altogether, our results indicated that Se exerted anti-tumor effects in vivo at least partially by inhibiting angiogenic factors.

Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer MDR cell line

“…In contrast, the remaining selenocompounds (2-7) were non-selective, with the exception of 4 on Colo 320 MDR cells (SI = 2.3, slightly selective). None of the four reference compounds evaluated (12)(13)(14)(15) showed cytotoxic activity in any of the cell lines assayed: the human colon adenocarcinoma cells (Colo 205 and Colo 320, Table 3), the non-tumoral MRC-5 cells (Table 3) and the mouse T-lymphoma cells (PAR and MDR, data now shown). In the case of the pair selenoanhydride (1) -phthalic anhydride (12), results highlight the importance of the selenium atom to the biological activity.…”

miR‐497 induces apoptosis by the IRAK2/NF‐κB axis in the canine mammary tumour

“…The CMT1211 and CMT7364 canine mammary tumour cell line were provided by Professor Degui Lin of China Agricultural University and have been used in the study of canine mammary tumours 17,18 . Human HEK293 cells were purchased from American Tissue Culture Collection (ATCC, Rockville, MD).…”

Angiogenesis‐related gene expression profile in clinical cases of canine cancer

“…; Li et al . ). However, although several studies have reported on the expression of angiogenesis‐related genes in canine tumours, few studies have compared the expression profiles of angiogenesis‐related genes in normal and tumour tissues.…”

“…In the field of veterinary oncology, the importance of angiogenesis in tumour progression has been recognised (Restucci et al 2003;Millanta et al 2006;Yonemaru et al 2006;Camacho et al 2014), and several therapies targeting tumour angiogenesis are being used for some tumour types (Scharf et al 2013;Li et al 2016). However, although several studies have reported on the expression of angiogenesisrelated genes in canine tumours, few studies have compared the expression profiles of angiogenesisrelated genes in normal and tumour tissues.…”