Figure 4.

LDHA/PDHA1 Loss Modulate Therapeutic Sensitivity in HNSCC Cells. (A) Decreased IC50 for clinical chemotherapeutic agent CDDP, 5-FU and paclitaxel in LDHA deficient HNSCC cells as higher IC50 was detected in response to PDHA1 loss. This effect is probably regulated via (B) alterations of ALDH activity, (C) ABCC family and (D) Nanog/Oct4 mRNA expression or/and (E) differential changes of cellular differentiation marker involucrin protein by Western blot and immunofluorescence staining analysis in LDHA/PDHA1-silencing HNSCC cells. (F) LDHA/PDHA1 reporter systems were established to explore metabolism-mediated anti-cancer molecules. Dietary anti-neoplastic agents curcumin, EGCG, AMPK activator metformin and herbal extract compound silibinin, but not CDDP, suppressed LDHA promoter activity and activated PDHA1 promoter activity in FaDu and OECM-1 cells. Data are presented as mean ± SEM (N≥3). ***P < .001; **P < .01; *P < .05.