Down-Regulation of CYP3A4 by the K_Ca1.1 Inhibition Is Responsible for Overcoming Resistance to Doxorubicin in Cancer Spheroid Models.

ABSTRACT: The large-conductance Ca²⁺-activated K⁺ channel, K_Ca1.1, plays a pivotal role in cancer progression, metastasis, and the acquisition of chemoresistance. Previous studies indicated that the pharmacological inhibition of K_Ca1.1 overcame resistance to doxorubicin (DOX) by down-regulating multidrug resistance-associated proteins in the three-dimensional spheroid models of human prostate cancer LNCaP, osteosarcoma MG-63, and chondrosarcoma SW-1353 cells. Investigations have recently focused on the critical roles of intratumoral, drug-metabolizing cytochrome P450 enzymes (CYPs) in chemoresistance. In the present study, we examined the involvement of CYPs in the acquisition of DOX resistance and its overcoming by inhibiting K_Ca1.1 in cancer s

SUBMITTER: Ohya S 

PROVIDER: S-EPMC10648085 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature