Differential Responses of Parental and Cisplatin-Resistant Primary and Metastatic Head and Neck Squamous Cell Carcinoma Cells to Porphyromonas gingivalis Lipopolysaccharide

Background/Objectives: Chronic periodontal inflammation and Porphyromonas gingivalis (Pg)-derived inflammatory signals have been implicated in head and neck squamous cell carcinoma (HNSCC) progression and chemotherapy responsiveness. However, whether acquired cisplatin resistance alters subsequent responses of HNSCC cells to Pg-derived lipopolysaccharide (Pg-LPS) remains unclear. This study investigated the responses of parental and cisplatin-resistant HN18 and HN17 HNSCC cells to Pg-LPS stimulation. Methods: Cisplatin-resistant sublines (HN18R and HN17R) were established by repeated exposure to cisplatin at the half-maximal inhibitory concentration (IC50). Basal proliferation was compared between parental and resistant cells, followed by Pg-LPS stimulation (0.25–2 μg/mL). Cell proliferation was assessed by MTT assay, interleukin-6 (IL-6) concentrations by enzyme-linked immunosorbent assay, nitrite concentrations as an indirect indicator of nitric oxide (NO) production by Griess assay, and matrix metalloproteinase (MMP)-2 and MMP-9 activity by gelatin zymography. Results: HN18 cells were less sensitive to cisplatin than HN17 cells, with IC50 values of approximately 60 and 30 μM, respectively. Following acquisition of cisplatin resistance, HN18R showed lower basal proliferation than HN18, whereas HN17R showed higher basal proliferation than HN17. Pg-LPS elicited distinct responses in the two resistant sublines. HN18R cells showed lower proliferation and nitrite concentrations but higher pro-MMP-2 band intensity than HN18. In contrast, HN17R exhibited greater proliferation and IL-6 concentration but lower pro-MMP-2 band intensity than HN17. No distinct MMP-9 activity was detected. Conclusions: Acquired cisplatin resistance was associated with distinct, lineage-dependent responses to Pg-LPS, highlighting heterogeneous responses of cisplatin-resistant HNSCC cells to periodontal inflammatory stimulation.