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Fig. 7 | Cancer & Metabolism

Fig. 7

From: Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments

Fig. 7

SCD is essential for orthotopic tumour growth of prostate cancer cells. a DU145 cells expressing inducible shRNAs targeting SCD (shSCD #2) or scrambled control (shNTC) were injected orthotopically into the frontal lobe of the prostate of immunocompromised mice (nu/nu). Gene silencing was induced 10 days post-implantation by treatment with doxycycline (DOX). Tumour growth was followed using intravital bioluminescence imaging of luciferase-positive cancer cells. Data represent mean bioluminescence ± SEM of eight mice per treatment group. Statistical comparisons were performed using Student t-tests (***p ≤ 0.0001). b Images of bioluminescence in mice at day 25 after initiation of doxycycline treatment. c Representative images of tumours detected by 3D ultrasound imaging 27 days after initiation of doxycycline treatment. d Survival curves of mice orthotopically implanted with prostate cancer cells and treated with doxycycline from day 10 onwards (early, red line) or day 47 onwards (late, blue line) compared to controls. Statistical comparisons were performed using the log-rank (Mantel-Cox) test (**p ≤ 0.001). e Schematic representation of the vulnerability of cancer cells towards inhibition of FA desaturation under the metabolically compromised conditions of the tumour microenvironment. Our data suggest that tumour cells are exposed to conditions of reduced availability of exogenous lipids, making them vulnerable towards inhibition of FA desaturation. Inhibition of SCD causes relative accumulation of saturated FAs and disturbs CL compositions resulting in release of cytochrome C, reduced mitochondrial activity, enhanced sensitivity towards chemotherapeutic drugs and reduced tumour growth

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