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. 2013 Oct 8;5(12):1821–1834. doi: 10.1002/emmm.201302654

Figure 5.

Tumour growth inhibiting effect of combining netrin-1 interference and Doxorubicin.

  1. TRAP-netrinUnc5A potentiates Doxorubicin anti-cancer effect in a preclinical animal model. A549R cells were engrafted in 7-weeks old female athymic nude mice. Once tumours reached a 100 mm3-volume, mice were treated intraperitoneally with TRAP-netrinUNC5A (20 mg/kg), Doxorubicin (2 mg/kg) or with a combination of both drugs, twice a week for two weeks. As a control, mice were injected with PBS. Histogram represents tumour volume growth for each group as a function of days post-xenografts. While both drugs alone were not able to reduce tumour growth, combination of TRAP-netrinUNC5A and Doxorubicin treatment significantly reduced tumour growth.

  2. Quantification of apoptosis by caspase-3 activity assay on xenografts lysates analysed after 2 days of treatment. Data are means of caspase-3 activities in four xenograft tumour lysates for each condition.

  3. Quantification of netrin-1 expression on engrafted A549R cells from nude mice treated with PBS or Doxorubicin for 48 h. Netrin-1 expression was normalized using hypoxanthine-guanine phosphoribosyltransferase (HPRT) and TATA binding protein (TBP) genes, used as housekeeping genes. Data are means of total RNA extracted from seven animals for each group. Median, min and max values, as well as the upper and lower quartiles, are indicated.

  4. Quantification of netrin-1 expression in non-tumoural tissues from nude mice treated as above. The indicated tissues were taken 48 h after treatment and total RNA was extracted. Netrin-1 expression was normalized using 60S acidic ribosomal protein P2 (RPLP2) gene, used as housekeeping gene. *, p < 0.05; **, p < 0.01; ***, p < 0.001; DoxoR, Doxorubicin.

Figure 5