Explore the Function and Mechanisms of Triptolide in Tenascin-C Mediated Migration and Gemcitabine Resistance in...

The extracellular matrix protein Tenascin-C (TNC) is known to promote the development of pancreatic cancer. The current study investigated the effect and mechanism of Triptolide (TP), a monomer component extracted from the traditional Chinese herb Tripterygium wilfordii, on TNC expression and TNC-mediated malignant behaviors in human pancreatic cancer.

Database analysis showed TNC expression clusters in pancreatic tissue and the prognostic effect. RT-qPCR and ELISA were performed to detect the TNC expression levels after TP treatment. The miR-sequencing results of TP combined with RT-qPCR were used to screen the potential miRNAs of TP that regulate TNC. The migration and apoptosis ability were detected by scratch assay and flow cytometry.

High levels of TNC are associated with poor outcomes in pancreatic cancer patients. TP suppresses both TNC mRNA levels and protein secretion in a dose-dependent manner. Additionally, TNC mediated migration and gemcitabine resistance were remarkably decreased following TP treatment. In addition, TP significantly inhibited the expression of miR-144, miR-654, and miR-520, and the inhibition of TNC expression by TP was reversed by the miR-144 antagomir. Furthermore, TP could suppress migration and gemcitabine resistance by regulating the miR-144/TNC axis, thereby inhibiting the pancreatic cancer progression.

TP may represent a promising therapeutic candidate for pancreatic cancer by targeting the stroma, with its effects mediated through the miR-144/TNC axis.