ABSTRACT
Aim To investigate the effect of Rhein on the movement and invasiveness of human ovarian carci-noma cells with directional high lymphatic metastasis SKOV3-PM4 cells and explore the role of Rac1/LIMK1/cofilin signaling pathway. Methods Migration assay and invasion assay were used to observe the effect of Rhein on the metastatic and invasive ability of SK-OV3-PM4 cells in vitro. The effect of Rhein on the morphology and cytoskeleton ultrastructure of ovarian cancer cells was observed by laser scanning confocal microscope and scanning electron microscope. The protein expression level of Rac1,LIMK1,PAK1 and co-filin were detected by Western blot, respectively. Re-sults Rhein inhibited the abilities of cell invasion and migration of SKOV3-PM4 cells,and the inhibitory rate increased along with the increase of the concentration and treatment duration. After treated with 8. 80 μmol· L-1 ,17. 60 μmol · L-1 , 26. 40 μmol · L-1 of Rhein for 24 h,the abilities of migration and invasion of SK-OV3-PM4 cells were inhibited ( P <0. 05 ); the mor-phology and cytoskeleton ultrastructure of SKOV3-PM4 cells were changed, cellular pseudopod reduced, cell microfilament fractured and its distribution disordered, plasma membrane was uneven and cell gap widened . After treatment of Rhein and Rac1 inhibitor , Rac1 protein expression and the expression of P-LIMK1 , P-PAK1 and P-cofilin notably decreased in a dose-de-pendent manner compared with the control group ( P<0. 05 ) . After Rhein and Rhein plus Rac1 inhibitor treatment ,P-LIMK1, P-cofilin, P-PAK1 protein levels of SKOV3-PM4 cells significantly decreased compared with the control group , and the group of Rac1 inhibi-tor plus Rhein treatment, the phosphorylated protein decreased more significantly ( P <0. 05 ) . After Rac1 activator plus Rhein treatment, phosphorylated protein expression of P-LIMK1 ,P-PAK1 and P-cofilin upregu-lated significantly ( P <0. 05 ) . Conclusions Rhein may be a potential inhibitor of Rac1 and can inhibit the migrating and invasive capabilities of directional high lymphatic metastasis SKOV3-PM4 cells through down-regulating the phosphorylation of Rac1/LIMK1 /cofilin pathway associated protein.
ABSTRACT
As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efifcacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Speciifcally, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surifng, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.
ABSTRACT
Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the major histological types of non-small cell lung carcinoma (NSCLC). Although both SCCs and ACs have been characterized histologically and clinically, the precise mechanisms underlying their migration and invasion are not yet known. Here, we address the involvement in NSCLC of the p21-associated kinase1 (Pak1)/LIM kinase1 (LIMK1)/cofilin pathway, which recently has been reported to play a critical role in tumor migration and invasion. The Pak1/LIMK1/cofilin pathway was evaluated in tumors from SCC (n=35) and AC (n=35) patients and in SCC- and AC-type cell lines by western blotting, immunohistochemistry, and in vitro migration and invasion assays. The levels of phosphorylated Pak1, LIMK1, and cofilin in lung tumor tissues from SCC patients were increased as compared to normal tissues. In addition, immunohistochemistry showed greater expression of phosphorylated cofilin in SCC tissues. Expression of phosphorylated Pak1 and LIMK1 proteins was also significantly higher in SCC-type cells than in AC-type cells. Moreover, migration and invasion assays revealed that a higher percentage of SCC type cells exhibited migration and invasion compared to AC type cells. Migration was also decreased in LIMK1 knockdown SK-MES-1 cells. These findings suggest that the activation of the Pak1/LIMK1/cofilin pathway could preferentially contribute to greater tumor migration and invasion in SCC, relative to that in AC.