gw-4869 and Colorectal-Neoplasms

Calcium‑dependent activator protein for secretion 1 (CAPS1) has been reported to promote metastasis in colorectal cancer (CRC), however, the underlying mechanisms have not yet been elucidated. The present study revealed that exosomes derived from CAPS1‑overexpressing CRC cells could enhance the migration of normal colonic epithelial FHC cells. GW4869, an inhibitor of exosomes, could attenuate the migration of FHC cells. Furthermore, liquid chromatography‑mass spectrometry (LC‑MS) and bioinformatics analysis demonstrated that overexpression of CAPS1 could alter the expression pattern of exosomal proteins involved in cell migration. Bone morphogenetic protein 4, which may serve vital roles in the process of CAPS1‑induced cell migration, was downregulated in the exosomes. In summary, the present results demonstrated that CAPS1 promotes cell migration by regulating exosomes. Inhibiting the secretion of exosomes may be helpful for the treatment of patients with metastatic CRC.

Topics: Aniline Compounds; Apoptosis; Benzylidene Compounds; Bone Morphogenetic Protein 4; Calcium-Binding Proteins; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Computational Biology; Drug Screening Assays, Antitumor; Exosomes; Gene Expression Regulation, Neoplastic; HEK293 Cells; HT29 Cells; Humans; Microscopy, Electron; Protein Interaction Mapping; Vesicular Transport Proteins

Oxaliplatin is commonly used in managing malignancy, including colorectal cancer. While treatment often fails due to decreased drug sensitivity, the mechanisms involved are not clear. In this study, we investigate how exosomal miR-19b participates in oxaliplatin sensitivity and then prove that miR-19b down-regulates oxaliplatin sensitivity of sw480 cells. We found that suppressing the secretion of exosomal miR-19b with gw4869 promotes sw480 cell oxaliplatin sensitivity. Our combined results demonstrate for the first time that miR-19b regulates the oxaliplatin sensitivity of sw480 cells and provides a unique mechanism mediated by gw4869 to modulate oxaliplatin sensitivity by suppressing exosomal miR-19b release.

Topics: Aniline Compounds; Benzylidene Compounds; Cell Line, Tumor; Colorectal Neoplasms; Drug Resistance, Neoplasm; Exosomes; Humans; MicroRNAs; Oxaliplatin