Octreotide-Paclitaxel Conjugate Reverses Paclitaxel Resistance by p38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in A2780/Taxol Human Ovarian Cancer Cells
Li-li Fan, Xi Chen, Xiao-yu Zhang, Ze-min Li, Xue-mei Fan, Yang Shen
Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China (mainland)
Med Sci Monit 2020; 26:e922612
Available online: 2020-06-24
Platinum plus paclitaxel is a first-line chemotherapy for ovarian cancer. Platinum resistance is a hot topic for many scholars, but drug resistance caused by paclitaxel is also a topic of concern. Currently, scholars believe that inhibition of MAPK signaling pathway may be an effective way to reverse the drug resistance of tumor paclitaxel.
MATERIAL AND METHODS: A2780/Taxol cells or nude mice were divided into 8 groups: control group, OCT (octreotide) group, OC (octreotide+cyclosomatostatin) group, PTX (paclitaxel) group, PO (paclitaxel+octreotide) group, POC (paclitaxel+octreotide+cyclosomatostatin) group, P-O (octreotide-paclitaxel conjugate) group, and P-OC (octreotide-paclitaxel conjugate+cyclosomatostatin) group. The phosphorylation level of p38 MAPK and the expression level of vascular endothelial growth factor (VEGF) were determined by western blot. Flow cytometry was used to discover the apoptosis of A2780/Taxol cells and xenografts. The expression of class III beta-tubulin was detected by immunohistochemistry.
RESULTS: Octreotide-paclitaxel conjugate inhibited phosphorylation of the p38MAPK signal pathway, decreased the expression of downstream VEGF, and increased the apoptosis of drug-resistant cancer cells. In addition, it reduced the expression of class III beta-tubulin protein and increase the sensitivity of drug-resistant cells to paclitaxel. All these effects of octreotide-paclitaxel conjugate were cancelled by cyclosomatostatin.
CONCLUSIONS: Octreotide-paclitaxel conjugate can reverse the paclitaxel resistance of A2780/Taxol human ovarian cancer cells by inhibiting the activity of p38 MAPK signaling pathway.
Keywords: Drug Resistance, Neoplasm, Linoleic Acids, Conjugated, Ovarian Neoplasms, paclitaxel, somatostatin