{"doi":"10.3390/cells12071056","title":"ABCB1 and ABCG2 Overexpression Mediates Resistance to the Phosphatidylinositol 3-Kinase Inhibitor HS-173 in Cancer Cell Lines","abstract":"Constitutive activation of the phosphoinositide-3-kinase (PI3K)/Akt signaling pathway is crucial for tumor growth and progression. As such, this pathway has been an enticing target for drug discovery. Although HS-173 is a potent PI3K inhibitor that halts cancer cell proliferation via G2/M cell cycle arrest, the resistance mechanisms to HS-173 have not been investigated. In this study, we investigated the susceptibility of HS-173 to efflux mediated by the multidrug efflux transporters ABCB1 and ABCG2, which are two of the most well-known ATP-binding cassette (ABC) transporters associated with the development of cancer multidrug resistance (MDR). We found that the overexpression of ABCB1 or ABCG2 significantly reduced the efficacy of HS-173 in human cancer cells. Our data show that the intracellular accumulation of HS-173 was substantially reduced by ABCB1 and ABCG2, affecting G2/M arrest and apoptosis induced by HS-173. More importantly, the efficacy of HS-173 in multidrug-resistant cancer cells could be recovered by inhibiting the drug-efflux function of ABCB1 and ABCG2. Taken together, our study has demonstrated that HS-173 is a substrate for both ABCB1 and ABCG2, resulting in decreased intracellular concentration of this drug, which may have implications for its clinical use.","journal":"Cells","year":2023,"id":347619,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":503206,"name":"Cheng‐Yu Hung","orcid":"0000-0003-4158-5079","position":1,"is_corresponding":false},{"id":1089491,"name":"Ya‐Ju Hsieh","orcid":"0000-0003-3853-4342","position":2,"is_corresponding":false},{"id":739728,"name":"Megumi Murakami","orcid":"0000-0002-3920-2166","position":3,"is_corresponding":false},{"id":460359,"name":"Yang-Hui Huang","orcid":null,"position":4,"is_corresponding":false},{"id":1089971,"name":"Tsung-Yao Su","orcid":null,"position":5,"is_corresponding":false},{"id":459361,"name":"Tai‐Ho Hung","orcid":"0000-0003-2354-7060","position":6,"is_corresponding":false},{"id":503207,"name":"Jau‐Song Yu","orcid":"0000-0002-4295-983X","position":7,"is_corresponding":false},{"id":459364,"name":"Yu‐Shan Wu","orcid":"0000-0003-4027-0710","position":8,"is_corresponding":false},{"id":334608,"name":"Suresh V. Ambudkar","orcid":"0000-0002-2639-4955","position":9,"is_corresponding":false},{"id":459360,"name":"Chung‐Pu Wu","orcid":"0000-0002-2434-3361","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T01:12:01.859977Z","pmid":"37048130","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}