Fig. 4.

TPL sensitized GC cells to SN38 and reversed the SN38 resistance induced by co-culture with CAFs. a Cell viability of MKN45, BGC-823 and CAFs after treated with different concentrations of SN38 combined with/without 12.5 nM TPL for 48 h. b Combination index (CI) analysis of TPL and SN38 combinational therapy in MKN45, BGC-823 and CAFs. c, d Cell cycle distributions of MKN45 and BGC-823 cells after treated with TPL, SN38 or a combination of TPL and SN38 for 24 h. e Western Blot assay of cyclin D1 and cyclin B1 of MKN45 and BGC-823 with different treatments. f Illustration of mono-culture and co-culture models. In the mono-culture model, GC cells were cultured individually. Transwell chambers were utilized in the co-culture model: CAFs were cultured in the upper chamber; whereas, GC cells were cultured in the lower chamber. g, h Apoptotic analysis of BGC-823 and MKN45 cells after the treatment of TPL, SN38 or a combination of SN38 and TPL for 24 h in the co-culture and mono-culture model, respectively. i Western Blot analysis of PARP, cleaved PARP and NF-κB/p65 in the BGC-823 and MKN45 cells which were treated with TPL, SN38 or a combination of TPL and SN38 for 24 h in the co-culture model. All data are presented as mean ± SD. Unpaired student’s t-test was used to analyze the data. (*p < 0.05; **p < 0.01; ***p < 0.001)