05 in A and C; P < 0.01 in D and E). Effects of PDCD4 on MHCC-97H cell migration and invasion In the migration assay, the average

number of migrated cells per field of the MHCC-97H -PDCD4 group (Group1) was 27.20 ± 7.26, which was much lower than that of the MHCC-97H -vector group (Group2) (161.80 ± 17.06) or the MHCC-97H group (Group3) (194.60 ± 30.83) (Fig. 3D). The average number of migrated cells in the invasion assay was 19.0 ± 3.18, 64.40 ± 9.61 and 69.80 ± 12.32 for the Group1, Group2 and Group3, respectively (Fig. 3E). The difference was significant AZD6094 in vitro between Group1 and Group2 or Group3 (n = 5, P < 0.01). There is no difference between Group2 and Group3. Discussion PDCD4 was originally found to be an apoptosis-associated gene in mouse cells. PDCD4 expression was found to be up-regulated in cells treated with various apoptosis-inducing agents such as topoisomerase inhibitors, corticosteroids and cytokine deprivation[29]. The function

of PDCD4 in the course of programmed cell death remains unclear. Later studies showed that PDCD4 was a suppressor of tumor cell transformation. The expression levels of PDCD4 were reduced in many human progressed carcinomas[7]. A study on human HCC showed that expression level of PDCD4 protein was much lower in HCC tissues tested than that of the corresponding noncancerous liver[30]. In this study, we showed that higher metastatic potential HCC cells expressed lower level of PDCD4. The expression levels of PDCD4 were inversely correlated with the metastasis potentials of HCC cells. This result is consistent with the previous JNK-IN-8 research buy BCKDHA findings. We also demonstrated that the MHCC-97H cell proliferation

rate was remarkably decreased and the cell apoptosis rate was significantly increased after transfection with the PDCD4 gene. Cell cycle analysis showed that transfection of PDCD4 gene increase the percentage of both G1 and G2. Data of our results suggest that PDCD4 might promote cell cycle arrest in phase of G1 and in G2 and further block the cell proliferation. It is known that PDCD4 is a binding partner of the eukaryotic Omipalisib clinical trial translation initiation factor 4A (eIF4A). By binding to eIF4A, PDCD4 can directly inhibit translation initiation and then delay the process of protein synthesis. A study on Bon-1 carcinoid cells showed that PDCD4 not only suppressed the transcription of the mitosis-promoting factor cyclin-dependent kinase 1(CDK1)/cdc2, but also decreased the expression of CDK4/6[31]. CDK1 and CDK4/6 are are directly involved in cell cycle control. Decrease of CDK1 or CDK4/6 promotes cell cycle arrest in G1 or G2 phase and further inhibits proliferation of cells[32]. PDCD4 inhibits the activity of c-Jun N-terminal kinase (JNK), blocks the JNK signaling pathway and consequently decreases the activation of c-Jun and AP-1-dependent transcription[8]. Many genes regulated by AP-1 are important modulators of invasion and metastasis.