Tunicamycin enhances the suppressive effects of cisplatin on lung cancer growth through PTX3 glycosylation via AKT/NF-κB signaling pathway.

ABSTRACT

Long pentraxin­3 (PTX3) is an inflammatory molecule related to cancer proliferation, invasion, and metastasis. Many studies have highlighted the significance of glycosylated molecules in immune modulation, inflammation and cancer progression. Moreover, aberrant glycosylation of cancer cells is linked to chemoresistance. This study aimed to develop effective therapeutic strategies for deglycosylation of PTX3 (dePTX3) in order to enhance chemosensitivity to cisplatin (Cis) in lung cancer treatment. The A549 and SPCA1 cells were used to determine the role of PTX3 glycosylation in lung cancer growth. Our results revealed that PTX3 was higher in both human lung cancer tissues and serum in comparison with control. Furthermore, we found that deglycosylated PTX3 (dePTX3) by tunicamycin (TM), which is N­glycan precursor biosynthesis blocker, and PNGase F significantly reduced the survival and migration of lung cancer cells. To further confirm this, we also generated glycosylation­site mutant of PTX3 (mPTX3) to characterize the loss of glyco­function. dePTX3 and TM enhanced the suppressive effects of Cis on lung cancer cell growth, migration and invasion compared to individual treatment. Treatment with a combination of TM and Cis significantly inactivated AKT/NF­κB signaling pathway and induced apoptosis. In conclusion, these findings suggest that PTX3 is an important mediator of lung cancer progression, and dePTX3 by TM enhances the anticancer effects of Cis. The deglycosylation in chemotherapy may represent a potential novel therapeutic strategy against lung cancer.