Inhibition of both SREBP1 and SREBP2 is required to prevent PDAC cell and tumor growth. A, Immunoblot of Pa03c wild-type, SREBF1 KO, SREBF2 KO, SREBF1/2 double KO cells for indicated antibodies. Membrane-enriched extracts (20 μg) were harvested and probed for SREBP1 and SREBP2. Calnexin served as a loading control. B, Wild-type (WT) Pa03c, SREBF1 KO, SREBF2 KO, SREBF1/2 double KO, and MBTPS1 KO cells were cultured in either 10% FBS or 1% FBS for 7 days. Media were changed every 3 days. Plates were stained with crystal violet and quantification is shown (n = 3 per group). For each cell line, growth was normalized to the 10% FBS condition. Statistical significance was determined using two-way ANOVA and Tukey HSD test. P values are indicated: *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001, ns, not significant. Error bar denotes SD. C, Nude mice were subcutaneously injected with 1 × 10⁶ Pa03c cells of the indicted genotype in both flanks (two tumors per mouse). Once visible, tumors were measured, and volume calculated. Each group contained five mice. Error bar denotes SD. D, Individual tumor volumes at day 25, n = 10 tumors per group. Statistical significance was determined using one-way ANOVA and Dunnett test. Error bar denotes SD.
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Ishida et al. (2024) studied this question.
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