TOFA suppresses ovarian cancer cell growth in vitro and in vivo.

A characteristic feature of cancer cells is the activation of de novo fatty acid synthesis. Acetyl­CoA carboxylase (ACC) is a key enzyme in fatty acid synthesis, accelerating the reaction that carboxylates cytosolic acetyl­CoA to form malonyl­CoA. ACC is highly expressed in several types of human cancer and is important in breast and prostate cancer cell growth. The aim of the present study was to investigate the effects of 5­tetradecyloxy­2­furoic acid (TOFA), an allosteric inhibitor of ACC, on the proliferation and cell cycle progression of the ovarian cancer cell lines COC1 and COC1/DDP. TOFA was found to be cytotoxic to COC1 and COC1/DDP cells with a 50% inhibitory concentration (IC50) of ~26.1 and 11.6 µg/ml, respectively. TOFA inhibited the proliferation of the cancer cells examined in a time­ and dose­dependent manner, arrested the cells in the G0/G1 cell cycle phase and induced apoptosis. The expression of the cell cycle regulating proteins cyclin D1 and cyclin-dependent kinase (CDK) 4, as well as the expression of the apoptosis­related proteins caspase­3 and Bcl­2, were detected by western blot analysis. Cyclin D1, CDK4 and Bcl­2 protein expression was inhibited by TOFA, while caspase­3 was cleaved and activated. To the best of our knowledge, the present study demonstrated for the first time that TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy.

In vivo biocompatibility of a plasma-activated, coronary stent coating.

Bare metal and drug-eluting coronary stents suffer an inherent lack of vascular cell and blood compatibility resulting in adverse patient responses. We have developed a plasma-activated coating (PAC) for metallic coronary stents that is durable, withstands crimping and expansion, has low thrombogenicity and can covalently bind proteins, linker-free. This has been shown to enhance endothelial cell interactions in vitro and has the potential to promote biointegration of stents. Using the rabbit denuded iliac artery model, we show for the first time that PAC is a feasible coating for coronary stents in vivo. The coating integrity of PAC was maintained following implantation and expansion. The rate of endothelialization, strut coverage, neointimal response and the initial immune response were equivalent to bare metal stents. Furthermore, the initial thrombogenicity caused by the PAC stents showed a reduced trend compared to bare metal stents. This work demonstrates a robust, durable, non-cytotoxic plasma-based coating technology that has the ability to covalently immobilize bioactive molecules for surface modification of coronary stents. Improvements in the clinical performance of implantable cardiovascular devices could be achieved by the immobilization of proteins or peptides that trigger desirable cellular responses.

Metformin inhibits the development and metastasis of ovarian cancer.

The aim of this study was to investigate the role of metformin in the regulation of development and metastasis of ovarian carcinoma cell lines in vitro and ovarian cancer in a nude mouse model in vivo. The effects of metformin on the ability of two high-metastatic potential human ovarian cancer cell lines (SKOV3 and HO8910-PM) to adhere, invade and migrate in vitro were observed by means of a cell adhesion test, cell invasion test and cell migration test. The size and number of the inoculated and metastatic tumours in vivo in a nude mouse were determined following intraperitoneal injection of metformin. Furthermore, the extent of angiogenesis (vWF) and macrophage infiltration in the tumour were determined. Proliferation, migration, invasion and adhesion of ovarian cancer cells were significantly inhibited (P<0.05) in a dose-dependent manner in vitro. In addition, metformin inhibited hepatic, intestinal and lung metastasis (P<0.05), with no weight loss in vivo, consistent with decreased expression of vWF and macrophage infiltration. Our data suggest that metformin inhibits the development and metastasis of ovarian cancer by reducing cellular-ECM interactions, neovascularisation and macrophage infiltration.

Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer.

Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration.