No abstract

Sorafenib, a pan-protein kinase inhibitor, inhibits the activity of various kinases (like vascular endothelial growth factor, platelet-derived growth factor, and rapidly accelerated fibrosarcoma) and clinically has been used to treat different human cancers. This study investigated its antitumor activity in ovarian cancer and the underlying molecular events. To achieve that, ovarian cancer SKOV-3 cells were treated with or without sorafenib (10 µM), transforming growth factor (TGF)-β1 (10 ng/mL), sorafenib (10 µM) + TGF-β1 (10 ng/mL), and TGF-β1 (10 ng/mL) + Ly2157299 (5 µM), followed by 8-Gy radiation. The cells were then subjected to cell viability, wound healing, Transwell, caspase-3 activity, and western blot assays. TGF-β1 treatment enhanced ovarian cancer cell epithelial–mesenchymal transition (EMT), whereas sorafenib and a selective TGF-β1 inhibitor Ly2157299 reversed tumor cell EMT, invasion, and expression of EMT markers (E-cadherin and vimentin). Sorafenib and Ly2157299 treatment also significantly reduced the tumor cell viability. Furthermore, both sorafenib and Ly2157299 significantly enhanced ovarian cancer cell radiosensitivity, as assessed by a caspase-3 activity assay. In conclusion, sorafenib inhibited ovarian cancer cell proliferation and mobility and induced tumor cell radiosensitivity. Molecularly, sorafenib could inhibit the TGF-β1-mediated EMT. Future studies will assess sorafenib anti-ovarian cancer activity plus TGF-β1 inhibitors in ovarian cancer in vivo.

Objective This study aimed to discuss clinical application value of contrast-enhanced ultrasonography on lesion skeletal muscle microcirculation and arterial perfusion reserve in type 2 diabetes mellitus and complicated microvessels. Methods Patients in the control group, type 2 diabetes mellitus (DM) group, diabetic microangiopathy (DM + MC) group underwent contrast-enhanced ultrasonography before and after temporary arterial occlusion to observe blood perfusion of gastrocnemius muscle; draw the time-intensity curve of arteriole, muscular tissue, and venule, and obtain perfusion parameters such as contrast agent arrival time and contrast agent transit time. Blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters were measured. Results Contrast agent transit time of the DM + MC group before arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of the DM + MC group after temporary arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of △artery-muscle, △artery-vein, and △muscle-vein of the DM group and control group and △artery-muscle of the DM + MC group after arterial occlusion was significantly shortened, when compared with that before arterial occlusion (P < 0.05). For △muscle-vein and △artery-vein contrast agent transit time in the DM + MC group, the difference was not statistically significant. By comparing blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters among the DM + MC group, DM group, and control group, the difference was statistically significant, and there was a good correlation. Conclusion Contrast-enhanced ultrasonography can be used to evaluate skeletal muscle microcirculation disturbance and arterial reserve function of patients who had type 2 diabetic microangiopathy.

No abstract