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An α-specific PI3K inhibitor improves chemotherapy efficacy by inhibiting hepatic stellate cell activation in liver cancer

ABSTRACT: The poor response to current systemic treatments in liver cancer has been associated with the activation of cancer-associated fibroblasts (CAFs). Herein, we aimed to investigate the effects of chemotherapy on hepatic stellate cells (HSCs), the main origin of CAFs in liver cancer. In vitro experiments demonstrated that cisplatin activated HSCs through a paracrine effect from HCC tumour cells while the mechanism remains unknown. RNA sequencing of human primary HSCs incubated in untreated or cisplatin-pretreated Huh7 conditioned medium revealed a PI3K signaling pathwayof HSC activation. Further analyses showed that PI3K pathway, especially PI3K p110a is crucial for HSC activation and by targeting PI3K p110a, HSC activation induced by cisplatin can be completely inhibited and improves cisplatin therapeutic efficacy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315789 | GEO | 2026/01/12

REPOSITORIES: GEO

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