In BMC Cancer this week, researchers in China report on the novel antitumor effects of rapamycin combined with bortezomib in hepatocellular carcinoma cells and an orthotopic tumor model. The team applied both drugs to liver cancer cell lines and found that the two worked together to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. "Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines," the authors write. "The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21, and apoptosis associated genes Bcl-2 [and] Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib." In mouse models, the drug combination inhibited tumor growth significantly more than either drug alone, and lung metastasis was also suppressed. "The combination treatment of rapamycin and bortezomib significantly inhibited tumor cell proliferation and tumor angiogenesis in vivo," the team adds. "The combination of rapamycin with bortezomib could be a novel and promising therapeutic approach to the treatment of HCC."
Also in BMC Cancer this week, researchers in Norway and the US report that increased expression of LCN2 is associated with aggressive features in endometrial cancer. The team analyzed levels of LCN2 in 256 endometrial cancer patients, and found that expression of LCN2 protein — which was found in 49 percent of the patients — was associated with nonendometrioid histologic type, nuclear grade 3, and solid tumor growth. "LCN2 expression was significantly associated with expression of VEGF-A," the authors write. "Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes." Increased LCN2 expression may be a marker of aggressive disease features and poor prognosis, they add.
Finally in BMC Cancer this week, researchers in South Korea describe a compound that inhibits angiogenesis. The compound, IDR-E804, is a derivative of indirubin, which is an extract of the indigo plant. The team tested the compound's effects on the proliferation, migration and capillary tube formation of human umbilical vein endothelial cells, induced by vascular endothelial growth factor, and on angiogenesis and tumor growth in a colon cancer mouse model. They found that IDR-E804 significantly decreased proliferation, migration and tube formation of VEGF-treated HUVECs, and inhibited tumor growth in the mice. "These data revealed that IDR-E804 is an inhibitor of angiogenesis and also provide evidence for the efficacy of IDR-E804 for anti-tumor therapies," they write.