<p>Resveratrol Suppresses Tumor Progression via Inhibiting STAT3/HIF-1α/VEGF Pathway in an Orthotopic Rat Model of Non-Small-Cell Lung Cancer (NSCLC)</p>

Abstract

Background: The STAT3/HIF-1α/VEGF pathway is associated with the development and progress of various tumors including NSCLC. The aim of the present study was to investigate whether resveratrol (RES) could suppress NSCLC progression via inhibiting the expressions of STAT3, HIF-1α, and VEGF in a nude rat model. Methods: Twenty-four nude rats were randomly divided into control, NSCLC, and NSCLC+RES groups. An orthotopic rat model of NSCLC was established. The animals in the NSCLC+RES group received the same operation as the NSCLC group and were intragastrically administered RES at 250 mg/kg/day for 12 weeks. Lung tissue samples were harvested for gross tumor burden measurement, histological examinations, RT-PCR, and Western blot assays. Results: In the NSCLC+RES group, significant decreases in lung weight index, lung tumor burden, STAT3/HIF-1α/VEGF mRNA, and protein levels were observed when compared with the NSCLC group (all P<0.05). The structural integrity of the lung was less affected and the apoptotic index was significantly higher in the NSCLC+RES group, when compared to the NSCLC group (P<0.05). Conclusion: RES suppresses NSCLC partly through inhibiting the expressions of STAT3, HIF-1α, and VEGF. The STAT3/HIF-1α/VEGF pathway might be a candidate drug target for developing new chemotherapy agents derived from RES for the treatment of NSCLC.

Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

“…It would be more meaningful should the anti-ATC efficacy can be proved in vivo. A body of evidence reveals the anticancer effects of resveratrol on a wide range of human malignancies in vitro [15,[50][51][52][53]. However, the corresponding in vivo data remain limited because trans-resveratrol can be efficiently metabolized to the less effective cis-resveratrol [54] and quickly eliminated from the body when it is administered systemically [55,56].…”

Resveratrol and Its Anticancer Effects

“…STAT3 is constitutively activated in many tumor types. Studies have shown that RSV effectively prevents cancer by inhibiting STAT3 expression (51). It also has an inhibitory effect on antiapoptotic mediators such as NF-kB, COX-2, phosphatidylinositol 3-kinase (PI3K), and mTOR (52).…”

Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

“…STAT3 is downregulated by resveratrol administration concomitantly with an attenuation of HIF-1α as well as VEGF levels in xenograft models of lung cancer [ 96 ], indicating the inhibitory function of resveratrol in hypoxia-mediated angiogenesis. In gastric cancer, resveratrol suppresses the HIF-1α/Hh signaling axis, reversing hypoxia-driven cell invasion and the EMT process [ 97 ].…”