AFP promotes cancer multidrug resistance through activating PI3K/Akt/NF-κB signaling pathway

Alpha-fetoprotein (AFP) has the biological function of promoting the malignant behaviors of liver Cancer cells, but how it regulates drug resistance in Cancer cells is still unclear. This study explore the effect of AFP on multidrug resistance (MDR) in cancers and its potential molecular mechanisms. RNA interference vector for AFP was constructed and transduced into the human liver Cancer cell line Bel 7402 (high AFP expression). However, the human cervical Cancer cell line HeLa (without AFP expression) was transduced with a overexpressing AFP vector. When these Cancer cells were treated with doxorubicin (ADM) and 5-fluorouracil (5-FU), cell survival rate was determined by MTT, Apoptosis by TUNEL, and colony formation by colony formation assay. The Cancer cells were treated with the PI3K/Akt pathway inhibitor LY294002, and the expression of drug resistance-related proteins MDR1, MRP1, BCRP, Livin, cIAP1, XIAP, Akt, p-Akt, p65, and p-p65 was detected by Western blotting. Bioinformatics analysis of the correlation between AFP regulation and intracellular signaling pathways was performed. The expression and localization of p65 were observed by immunofluorescence staining. Silencing AFP could increase the sensitivity of Bel7402 cells to ADM and 5-FU, whereas AFP overexpression caused resistance to ADM and 5-FU in HeLa cells. AFP was positively correlated with the PI3K/Akt/NF-κB signaling pathway, and there was a significant difference in the correlation between p65 and drug resistance genes. AFP regulates the expression of drug resistance-related genes by activating the PI3K/Akt/NF-κB signaling pathway. AFP plays a pivotal role in MDR of Cancer cells, the mechanism may be involved in activating the PI3K/Akt/NF-κB signaling pathway.

Alpha-fetoprotein; Cancer cells; Multidrug resistance; PI3K/Akt/NF-κB.