Cullin 4A (Cul4A) reportedly has oncogenic roles in several
cancer types by regulating
tumor suppressors through the ubiquitination and proteolysis of the
tumor suppressor. In addition, Cul4A is associated with chemosensitivity to
chemotherapy drugs. This study investigated the association between Cul4A and
lung cancer cell chemosensitivity to
paclitaxel, particularly with respect to the role of the p33 inhibitor of the growth 1 (p33ING1b)
tumor suppressor. The results showed that the Cul4A knockdown upregulated the p33ING1b expression in
lung cancer cells and increased the
lung cancer cell and mice
tumor xenograft chemosensitivity to
paclitaxel. The Cul4A knockdown also inhibited the growth and increased the apoptosis in the
tumor xenografts treated with
paclitaxel. Notably, the p33ING1b overexpression increased the
lung cancer cell chemosensitivity to
paclitaxel, but the p33ING1b knockdown reduced the chemosensitivity. A further analysis demonstrated that Cul4A regulates the expression of p33ING1b through
protein-
protein interactions, ubiquitination, and protein degradation. In conclusion, the present findings suggest that Cul4A mediates the chemosensitivity of
lung cancer cells to
paclitaxel by regulating p33ING1b. These findings may offer novel insights into future therapeutic strategies for
lung cancer that target Cul4A.