In this study, we investigated
purinergic receptor P2X7 and
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
inflammasome expressions, and their role in
head and neck cancer. We found upregulation of
purinergic receptor P2X7 and all NLRP3
inflammasome components in biopsied
head and neck squamous cell carcinoma tissues. Similarly, the expression of
purinergic receptor P2X7, apoptosis-associated speck-like
protein containing CARD, and pro-form
caspase 1 in A253 cells derived from
epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line. Active caspase-1 and its final product, active interleukin-1β, both increased in primed A253 cells stimulated with
purinergic receptor P2X7 agonists, while this elevated NLRP3
inflammasome activity was suppressed by
purinergic receptor P2X7 antagonists. However, we observed none of these effects in Human Salivary Gland cells. Inhibition of both NLRP3
inflammasome and
purinergic receptor P2X7 led to the significant cell death of primed A253 cells, but had no effect on the viability of primed HSG cells or the primary cultured human fibroblast cells. Furthermore, inhibition of either
purinergic receptor P2X7 or NLRP3
inflammasome decreased invasiveness of A253, and this effect became more evident when both
purinergic receptor P2X7 and NLRP3
inflammasome were simultaneously blocked. Therefore, it is concluded that the
purinergic receptor P2X7 and the activation of NLRP3
inflammasome play important roles in the survival and invasiveness of
head and neck squamous cell carcinoma in humans.