Research progress of plant-derived chemical compounds for overcoming pancreatic cancer drug resistance

Table 1 Summary of multidrug resistance proteins in pancreatic cancer

	Location	Expression trend	Primary function in drug resistance	Ref.
ABC	Barrier-protected tissues (gut, blood-brain barrier, liver, kidney)	Upregulated	Pump hydrophobic drugs out of cells to reduce intracellular concentration and transport anionic compounds such as topoisomerase inhibitors	[64-70,79,80]
P-gp	Intestinal epithelium, liver, kidney, hematopoietic system	Upregulated	ATP-dependent efflux of chemotherapeutic agents, reducing their cytotoxic efficacy	[71,81-84]
LRP	Excretory and immune tissues	Upregulated	Mediates active exclusion of drugs via nuclear export and compartmentalization mechanisms	[72-74,85-87]
Topo II	Highly proliferative tissues (hematopoietic system, intestinal crypts, germ cells), with Topo IIα dominant in cycling cells and Topo IIβ in post-mitotic cells (e.g., neurons)	Downregulated	Alterations in Topo II expression levels or activity downregulation of expression: Tumor cells reduce the expression of Topo IIα (the primary target of chemotherapeutic agents), reducing the number of available drug-binding sites. Topo II gene mutations: Mutations within drug-binding domains (e.g., the ATP- or DNA-binding regions) can impair the affinity between the enzyme and its inhibitors	[75,76,88,89]
GSTs	Detoxifying organs (liver, kidney)	Upregulated	Conjugate GSH with electrophilic compounds, reducing drug-induced oxidative stress	[77,78,90-92]

ABC: ATP-binding cassette; P-gp: P-glycoprotein; LRP: Lung resistance-related protein; Topo II: Topoisomerase II; GSTs: Glutathione S-transferases; GSH: Glutathione.