English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Inactivation of the   TP 53  tumor suppressor gene is essential during cancer development and progression. Mutations of   TP 53  are often missense and occur in various human cancers. In some fraction of wild‐type (wt)   TP 53  tumors, p53 is inactivated by upregulated murine double minute homolog 2 ( MDM 2) and  MDM 4. We previously reported that simultaneous knockdown of   MDM 4  and   MDM 2  using synthetic  DNA ‐modified si RNA s revived p53 activity and synergistically inhibited in vitro cell growth in cancer cells with wt   TP 53  and high  MDM 4 expression (wt  TP 53 /high MDM 4). In the present study,   MDM 4 /  MDM 2  double knockdown with the si RNA s enhanced 5‐fluorouracil (5‐ FU )‐induced p53 activation, arrested the cell cycle at G 1  phase, and potentiated the antitumor effect of 5‐ FU  in wt  TP 53 /high MDM 4 human colon ( HCT 116 and LoVo) and gastric ( SNU ‐1 and  NUGC ‐4) cancer cells. Exposure to 5‐ FU  alone induced  MDM 2 as well as p21 and  PUMA  by p53 activation. As p53‐ MDM 2 forms a negative feedback loop, enhancement of the antitumor effect of 5‐ FU  by   MDM 4 /  MDM 2  double knockdown could be attributed to blocking of the feedback mechanism in addition to direct suppression of these p53 antagonists. Intratumor injection of the   MDM 4/ MDM 2  si RNA s suppressed in vivo tumor growth and boosted the antitumor effect of 5‐ FU  in an athymic mouse xenograft model using  HCT 116 cells. These results suggest that a combination of   MDM 4 /  MDM 2  knockdown and conventional cytotoxic drugs could be a promising treatment strategy for wt  TP 53 /high MDM 4 gastrointestinal cancers.

Augmented antitumor activity of 5‐fluorouracil by double knockdown of MDM 4 and MDM 2 in colon and gastric cancer cells