Fig. 2: Disruption of SERPINB9 sensitized tumor to gemcitabine treatment through induction of granzymeB. | Nature Communications

Fig. 2: Disruption of SERPINB9 sensitized tumor to gemcitabine treatment through induction of granzymeB.

From: Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance

Fig. 2

a Expression of SERPINB9-GranzymeB complex, SERPINB9 and granzymeB in KPC-C2 SERPINB9 KO (KO) cells and KPC-C2 control vector (CV) cells. Cell proliferation of KPC-C2 KO cells versus KPC-C2 CV cells. n = 3 independent experiments. b In vivo tumor growth curves and tumor weights of KPC-C2 KO cells compared to KPC-C2 CV cells. n = 5 mice. c, d Abundance of Annexin V+ tumor cells (c) and immune cells (d, CD45+, CD8+, CD8+IFNγ, CD4+IFNγ, dendritic cells, myeloid-derived suppressor cells (MDSCs), M2 macrophages) in KPC-C2 KO tumors and KPC-C2 CV tumors. n = 4 independent samples. e Cell viability of KPC-C2 KO or KPC-C2 gemcitabine resistant (GEMR) KO cells versus their CV cells following treatments with different concentrations of gemcitabine. n = 6 independent experiments. The impact of SPB9 knockdown on the cytotoxicity of GEM in KPC-C5 WT or KPC-C5 GEMR (f) or human pancreatic cancer cells (g, Panc 02.03, MIA PaCa-2). n = 6 independent experiments. h Tumor growth curves of KPC-C2 KO and KPC-C2 CV tumors following treatment of PBS or PPOGEM polymer. n = 5 mice. i Protein expression of granzymeB (GzmB) and SPB-GzmB complex following treatment with different concentrations of gemcitabine in KPC-C2 cells. j Abundance of GzmB+ KPC-C5 cells, KPC-C2 SPB9 KO cells or PANC-1 cells following treatment with different concentrations of gemcitabine. n = 3 independent samples. k The impact of granzymeB knockdown on the cytotoxicity of GEM in KPC-C2 SPB9 KO cells. n = 6 independent experiments. l The proportion of Annexin V+ KPC-C2 SPB9 KO cells following treatment with PBS, GEM, or GEM+granzymeB inhibitor (GzmBi). n = 3 independent samples. Data are presented as mean ± s.e.m. in (a–g, h, j, k, l). Statistical analysis was performed by two-tailed Student’s t-test for comparison in (b, c, d), one-way ANOVA with Tukey’s post hoc test for comparison in (j, l), and two-way ANOVA with Tukey’s post hoc test for comparison in (b, h). Source data are provided as a Source Data file.

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