Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA-Damaging Agents.

ABSTRACT:

Purpose

We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs.

Experimental design

In a panel of cell lines, we investigated effects of pharmacologic and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38, and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo.

Results

Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in

SUBMITTER: Vasilevskaya IA 

PROVIDER: S-EPMC4573818 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature