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1.
Gene ; 823: 146275, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35189245

ABSTRACT

BACKGROUND: Silibinin, the principal flavonoid derived from milk thistle seeds, has been demonstrated to have strong inhibitory effects against human malignancies. The inhibitory function of silibinin on ovarian cancer, however, is not fully identified. In this essay, both in vivo and in vitro investigations were conducted to survey the silibinin's blocking effects on ovarian cancer. METHODS: The impacts of silibinin on two ovarian cancer cell lines, SKOV-3 and A2870, were determined by evaluating cell viability, migration, invasion, and apoptosis. Q-RT-PCR and western blotting techniques were carried out to explore the protein levels of signaling pathway markers. A mouse xenograft model was utilized to determine the silibinin efficacy in inhibiting tumor growth. RESULTS: After cell treatment with silibinin, cell viability, migration, and invasion were appreciably inhibited in cancer cell lines, but cell apoptosis was promoted. Also, silibinin reversed the epithelial-mesenchymal transition (EMT) mechanism by inducing E-cadherin expression and reducing N-cadherin and vimentin expression, suppressing the levels of regulators related to EMT such as Snail, Slug, and ZEB1 transcription factors, and also decreasing PI3K/AKT, Smad2/3, and ß-catenin intermediate molecules in vitro. Silibinin effectively ameliorated tumor growth in vivo. CONCLUSION: silibinin could be considered a potent agent against ovarian cancer based on the results.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Ovarian Neoplasms/drug therapy , Silybin/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Epithelial-Mesenchymal Transition/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Neoplasm Invasiveness , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Silybin/pharmacology , Xenograft Model Antitumor Assays
2.
EXCLI J ; 20: 601-613, 2021.
Article in English | MEDLINE | ID: mdl-33883985

ABSTRACT

Transforming Growth Factor-beta (TGF-ß) is dysregulated in colorectal cancer and there is growing evidence that it is associated with a poor prognosis and chemo-resistance in several malignances, including CRC. In this study we have explored the therapeutic potential of targeting TGF-ß using Tranilast in colon cancer. The anti-proliferative activity of Tranilast was evaluated in 2- and 3-dimensional cells. We used a xenograft model of colon cancer to investigate the activity of Tranilast alone or in combination with 5-FU on tumor growth using histological staining and biochemical studies, as well as gene expression analyses using RT-PCR and Western blotting. Tranilast alone or in combination with 5-FU inhibited tumor growth and was associated with a reduction of TGF-ß expression and CD31 positive endothelial cells. Histological evaluation showed that Tranilast increased tumor necrosis and reduced tumor density and angiogenesis. Tranilast increased MDA and ROS production. It was also found that Tranilast reduced total thiol concentration and reduced SOD and catalase activity. Tranilast plus 5-FU was also found to attenuate collagen deposition, reducing tumor fibrosis in tumor xenografts. Our results show that Tranilast, a TGF inhibitor, in combination with 5-FU reduces tumor growth by inhibiting fibrosis and inducting ROS, thus supporting this therapeutic approach in CRC treatment.

3.
J Cell Physiol ; 235(10): 6393-6403, 2020 10.
Article in English | MEDLINE | ID: mdl-32198752

ABSTRACT

Venous and arterial thrombosis are conditions that have a considerable burden if left untreated. The hypoxia-induced by the occluded vessel can disrupt the circulation of any organ, the cornerstone of treating thrombosis is rapid diagnosis and appropriate treatment. Diagnosis of thrombosis may be made by using laboratory tests or imaging techniques in individuals who have clinical manifestations of a thrombotic event. The use of serum micro ribonucleic acids (RNAs) has recently been applied to the diagnosis of thrombosis. These small RNA molecules are emerging as new diagnostic markers but have had very limited applications in vascular disease. Most of the articles provided various microRNAs with different levels of accuracy. However, there remains a lack of an appropriate panel of the most specific microRNA in the literature. The purpose of the present review was to summarize the existing data on the use of microRNAs as a diagnostic biomarker for venous thrombosis.


Subject(s)
Biomarkers/blood , MicroRNAs/blood , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Humans
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