ABSTRACT
BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5-7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.
Subject(s)
Animals , Female , Mice , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Neoplasm Metastasis/prevention & control , Antineoplastic Agents/pharmacology , Immunohistochemistry , Cell Line, Tumor , Mice, Inbred BALB CABSTRACT
The objective of the present study was to investigate the role of pentoxifylline (PTX) on remote testicular injury caused by unilateral hind limb ischemia/reperfusion of rats.
Twenty healthy male Wistar rats were allocated randomly into two groups: ischemia/reperfusion (IR group) and ischemia/reperfusion + pentoxifylline (IR+PTX group). Ischemia was induced by placement of a rubber tourniquet at the greater trochanter for 2h. Rats in IR+PTX group received PTX (40 mg/kg IP) before the reperfusion period. At 24h after reperfusion, testes were removed and levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and myeloperoxidase (MPO) activity were determined in testicular tissues. Three rats of each group were used for wet/ dry weight ratio measurement. Testicular tissues were also examined histopathologically under light microscopy.
Activities of SOD and CAT in testicular tissues were decreased by ischemia/ reperfusion (P<0.05). Significantly increased MDA levels in testicular tissues were decreased by PTX treatment (P<0.05). MPO activity in testicular tissues in the IR group was significantly higher than in the IR+PTX group (P<0.05). The wet/dry weight ratio of testicular tissues in the IR group was significantly higher than in the IR+PTX group (P<0.05). Histopathologically, there was a statistically significant difference between two groups (P<0.05).
According to histological and biochemical findings, we conclude that PTX has preventive effects in the testicular injury induced by hind limb ischemia/reperfusion.