Phthalocyanine and photodynamic therapy relieve albumin paclitaxel and gemcitabine chemoresistance in pancreatic cancer

Abstract

Pancreatic cancer (PCa) is a solid tumor with extremely high malignancy and poor prognosis. Chemotherapy is an important treatment option. Compared with gemcitabine alone, albumin paclitaxel plus gemcitabine (AG) is more effective in the treatment of advanced PCa. The NCCN guidelines also list AG regimen as one of the first-line recommended schemes for PCa. As for the mechanism of drug resistance of AG regimen, there is no relevant literature report at present. MIA PaCa-2 and BxPC-3, two PCa cell lines, were utilized to construct stable cell lines (AG-resistant cell lines) resistant to paclitaxel plus gemcitabine via gradually increased drug concentration of gemcitabine and albumin paclitaxel. AG-resistant cell lines are more malignant than parental cell lines in proliferation, invasion and chemoresistance. 5 genes, including ALDH3A1, ALDH3B1, CDA, MUC1, C15orf48 were found significantly high expression in AG-resistant cell lines. By utilizing PDB database and drugbank, a large-scale virtual screening of target drugs is carried out to screen for possible small molecule targeted drugs, and phthalocyanine was selected and proved to sensitize AG-resistant cell lines. We also validated the mechanism of phthalocyanine sensitizing chemoresistance, demonstrating that it leads to cell death by stimulating intracellular ROS level.