Targeting hypoxia-mediated chemo-immuno resistance by a hybrid NBDHEX-Pt(IV) prodrug via declining nuclear STING1-promoted AhR-CIN in human lung squamous cell carcinoma.

ABSTRACT: As found in human lung squamous cell carcinoma (LUSC), STING1 involved in ER-Golgi intermediate compartment (ERGIC) could coordinate immune responses to ectopic DNA triggered by DNA-targeted chemotherapy. ERGIC STING1 is considered to compete with nuclear STING1 to decline aryl hydrocarbon receptor (AhR)-chromosomal instability (CIN)-triggered chronic STING activation which could cause therapeutic resistance. Moreover, GSTP1 was proved to inhibit ERGIC-STING1 via promoting S-glutathione modification of STING1. Hence, a potent GSTP1-targeted Pt(IV) hybrid NBDHEX-DN604, was designed via conjugating a GSTP1 inhibitor NBDHEX to the axial position of Pt(IV) prodrug. As mentioned, hypoxia is mainly observed in malignant tumors and develops acquired drug resistance. In vitro bio-properties of hyp

SUBMITTER: Chen F 

PROVIDER: S-EPMC11985067 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature