Inhibition of the Arp2/3 complex represses human lung myofibroblast differentiation and attenuates bleomycin-induced pulmonary fibrosis.

Background And Purpose: The Arp2/3 multiprotein complex regulates branched polymerisation of the actin cytoskeleton and may contribute to collagen synthesis and fibrogenesis in the lung.

Experimental Approach: Expression of Arp2/3 components was assessed in human lung fibroblasts and in the bleomycin-induced pulmonary fibrosis model in mice. The Arp2/3 complex was repressed with the allosteric inhibitor CK666 and with interfering RNAs targeting the ARP2, ARP3 and ARPC2 subunits (siARP2, siARP3 and siARPC2) in CCD-16Lu human lung fibroblasts in vitro.

Enhancing tumor response to targeted chemotherapy through up-regulation of folate receptor α expression induced by dexamethasone and valproic acid.

Several folate-drug conjugates are currently undergoing clinical trials for application in oncology. However, the efficacy of folate-targeted therapy strongly depends on the folate receptor (FR) abundance at the surface of cancer cells. Recently, it has been postulated that up-regulation of FRα by means of chemo-sensitizing agents could enhance the anticancer activity of FR-drug conjugates.