Research on LCN2 interference to enhance the sensitivity of drug-resistant strains to Gemcitabine

This study was to observe the sensitivity of the resistant strains to gemcitabine by interfering with the LCN2. An AsPC-1 gemcitabine-resistant cell line (GEM-R) was generated. Based on GEM-R, a lentivirus-infected shRNA-transfected LCN2 cell line was established. The proliferation of LCN2-regulated GEM-R cells was evaluated using the CCK-8 test and the mRNA expression of Ki-67. The apoptosis level of each drug-resistant strain was detected by flow cytometry. The expression of Bax, Bcl-2, Akt, E-cadherin and Vimentin were detected by western blotting. A gemcitabine-resistant strain of AsPC-1 was successfully induced and constructed as an shRNA LCN2 strain based on GEM-R. It was also confirmed that interference of LCN2 expression enhanced the tumor inhibition and pro-apoptotic level of gemcitabine, increased the Bax/Bcl-2 value, and decreased p-Akt/Akt value. Meanwhile, the expression of E-cadherin was enhanced while the expression of Vimentin was decreased. This study confirmed that LCN2 affects gemcitabine sensitivity by participating in apoptosis and EMT processes, which may provide potential for overcoming gemcitabine resistance.