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. Author manuscript; available in PMC: 2024 Apr 1.
Published in final edited form as: Clin Cancer Res. 2024 Apr 1;30(7):1352–1366. doi: 10.1158/1078-0432.CCR-23-2043

Figure 5. Targeting endocytosis to enhance the impact of SAHA on NIS function in vivo.

Figure 5

A, RAI uptake in TPC-1-NIS and 8505C-NIS cells following AP2α1-siRNA depletion and SAHA treatment. Scr – scrambled control siRNA. B, Schematic of steps (1–4) used to examine the translatable potential of CQ and SAHA to enhance NIS function in vivo. C and D, Technetium-99m pertechnetate (99mTc) uptake (C; n = 4 -18) and NIS mRNA levels (D) in thyroid glands dissected from WT BALB/c mice administered with CQ and SAHA either alone or in combination. E-F, Same as D but relative TSHR, PAX8, NKX2-1, AP2A1 and PICALM mRNA levels in mouse thyroids. G, Distribution of 99mTc uptake across the indicated tissues harvested from WT BALB/c mice as described in B. Data presented as mean ± S.E.M.; ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001. H, Mechanistic impact of drug and siRNA targets modulating NIS retention at the PM. (1) Chloroquine, AP2 siRNA and PICALM siRNA inhibit endocytosis, (2) SAHA increases NIS transcription, (4) SAHA increases PICALM and AP2 transcription, and (4) Dynasore inhibits dynamin to block endocytosis. Combinatorial vorinostat and chloroquine treatment targeting both NIS transcription and endocytosis gives maximal NIS stimulation. Schematics created with BioRender.com.