Doxorubicin is reported to promote the nuclear translocation and DNA binding activity of NF B in HCC cells, but its biological consequence remains unknown. We found that doxorubi cin treatment significantly enhanced the NF B reporter activity, increased the levels of selleck chem inhibitor phosphorylated IB and p65, and induced the expression of c IAP1 Inhibitors,Modulators,Libraries and c IAP2. Importantly, compared with the negative control RNA duplex transfection, knockdown of p65 obviously increased the apoptosis rates in the doxorubicin treated cells. These data suggest that the doxorubicin triggered NF B activation is protective against apoptosis, which may reduce the chemosensitivity of HCC cells. We then explored the effect of miR 26b on the doxo rubicin triggered NF B activation.

The introduction of miR 26b significantly reduced the doxorubicin induced NF B reporter activity, compared with NC transfection. In addition, the doxorubicin triggered phos phorylation of IB and p65 was profoundly attenuated in miR 26b transfectants. Furthermore, the ectopic expression of miR 26b effectively decreased Inhibitors,Modulators,Libraries the doxorubicin stimulated expression of c IAP1 and c IAP2. Similar to the effect of miR 26b overex pression, knockdown of either TAK1 or TAB3 led to de creased NF B reporter activity in the doxorubicin exposed cells. These results suggest that miR 26b may inhibit the doxorubicin induced NF B activation by targeting TAK1 and TAB3. The above observations disclosed that the doxoru bicin triggered NF B activation protected cells from apoptosis and miR 26b significantly inhibited NF B signaling in HCC cells, we therefore further analyzed whether miR 26b could sensitize tumor cells to the doxorubicin induced apoptosis.

Compared with NC or non Inhibitors,Modulators,Libraries transfected cells, the doxorubicin induced apoptosis was much more pronounced in miR 26b transfectants, Inhibitors,Modulators,Libraries as determined by the morphological examination with DAPI staining. Moreover, immunoblotting assays re vealed more active caspase 3 in the doxorubicin exposed miR 26b tranfectants than the control cells. To verify the findings from gain of function study, loss of function analysis was performed. In response to doxorubicin treatment, anti miR 26b transfectants displayed reduced apoptosis rate, compared with the control group. Similar to the phenotype induced by miR 26b expression, the silencing of either TAK1 or TAB3 enhanced the rates of doxorubicin in duced apoptosis.

Inhibitors,Modulators,Libraries These findings imply that miR 26b may selleckchem Imatinib Mesylate inhibit the doxorubicin triggered NF B sig naling via targeting TAK1 and TAB3, which in turn sensi tizes HCC cells to the doxorubicin induced apoptosis. We and others have previously shown that miR 26b is downregulated in HCC. To confirm the associ ation of miR 26b with the anti apoptosis activity of NF B in vivo, we further evaluated the miR 26b levels and the apoptosis rates in human HCC specimens.