37 / 2021-07-27 20:08:10

IBP-I-K-3, a novel Kv10.1 channel inhibitor for hepatoma therapy

Liver cancer, Kv10.1; inhibitor; IBP-I-K-3; therapeutic.

Abstract: Liver cancer remains difficult to treat, owing to a paucity of drugs that target therapy. Targeting Kv10.1 channel may represent a strategy for the treatment of liver cancer. Therefore, the screening of Kv10.1 channel inhibitors with specificity and safety is very essential. Here, we identified that IBP-I-K-3, a natural compound, is a novel Kv10.1 channel inhibitor and it can suppress Kv10.1 current in a dose-dependent manner. The IC50 value of IBP-I-K-3 to Kv10.1 whole-cell current is 49.7 ± 0.9 nM. Further, IBP-I-K-3 concentration-dependently inhibited the proliferation and migration of HepG2, Huh-7 or Lo2-Kv10.1 cells, and the inhibition effect for HepG2 can be abolished by knockdown of the endogenous Kv10.1 with shRNA. In addition, we injected IBP-I-K-3 on xenograft mouse model which exhibited highly effective anti-tumor activity without adverse effects. In summary, IBP-I-K-3 can be used as a lead compound for anti-hepatocellular carcinoma drugs targeting Kv10.1.