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P-glycoproteins (P-gp) are an efflux transporter that pumps chemotherapeutic drugs out of cancer cells, resulting in chemotherapeutic resistance. Several types of long noncoding RNA (lncRNAs) have been identified in resistant cancer cells, including <jats:italic>ODRUL<\/jats:italic>, <jats:italic>MALAT1<\/jats:italic>, and <jats:italic>ANRIL.<\/jats:italic> The high expression level of <jats:italic>ODRUL<\/jats:italic> is related to the induction of <jats:italic>ATP-binding cassette (ABC)<\/jats:italic> gene expression, resulting in the emergence of doxorubicin resistance in osteosarcoma. lncRNAs are observed to be regulators of drug transporters in cancer cells such as <jats:italic>MALAT1<\/jats:italic> and <jats:italic>ANRIL.<\/jats:italic> Targeting P-gp expression using natural products is a new strategy to overcome cancer cell resistance and improve the sensitivity of resistant cells toward chemotherapies. This review validates the inhibitory effects of natural products on P-gp expression and activity using in silico molecular docking. <jats:italic>In silico<\/jats:italic> analysis showed that Delphinidin and Asparagoside-f are the most significant natural product inhibitors of p-glycoprotein-1. These inhibitors can reverse multi-drug resistance and induce the sensitivity of resistant cancer cells toward chemotherapy based on <jats:italic>in silico<\/jats:italic> molecular docking. It is important to validate that pre-elementary docking can be confirmed using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experimental data.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1511029","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:24:28Z","timestamp":1745558668000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of drug transporter inhibitors tied to long noncoding RNA in resistant cancer cells; a computational model -in silico- 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