The HIV protease and PI3K/Akt inhibitor nelfinavir does not improve the curative effect of fractionated irradiation in PC-3 prostate cancer in vitro and.

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The HIV protease and PI3K/Akt inhibitor nelfinavir does not improve the curative effect of fractionated irradiation in PC-3 prostate cancer in vitro and in vivo Steffi Liebscher, Lydia Koi, Steffen Löck, Michael H. Muders, Mechthild Krause Clinical and Translational Radiation Oncology Volume 2, Pages 7-12 (February 2017) DOI: 10.1016/j.ctro.2016.12.002 Copyright © 2016 The Authors Terms and Conditions

Fig. 1 In vitro effect of nelfinavir on PC-3: (A) A western blot for pAkt (S473) and ß-Actin and a western blot for Akt and β-Actin after incubation with nelfinavir for different incubation times are shown. The densitometry quantitations were evaluated by calculating pAkt:Akt, at which each value was set into relation with its corresponding ß-Actin value. The calculated ratios were normalized to control (DMSO) and listed below the western blots. This experiment was performed only once, as a test if the drug concentration and incubation time used by Pore et al. [22] can be adopted for our experiment (B) Clonogenic cell survival after different irradiation doses with or without nelfinavir incubation. All data were normalised to a surviving fraction of 1 at 0Gy irradiation dose. The colony formation assay was performed after treatment of PC-3 with 10μM nelfinavir or its solvent DMSO for 1h. The medium was exchanged before irradiation. Three independent experiments were performed. Means with SEM are indicated. The curve fitting was done using the linear-quadratic model. Curve fits were compared using F-test. (C) Corresponding to (B) the plating efficiency at 0Gy is shown without normalisation. Plating efficiencies were compared using the t-test. Clinical and Translational Radiation Oncology 2017 2, 7-12DOI: (10.1016/j.ctro.2016.12.002) Copyright © 2016 The Authors Terms and Conditions

Fig. 2 In vivo effect of nelfinavir on PC-3: (A) Relative tumour volumes of PC-3 xenografts after treatment with nelfinavir (80mg/kg body weight) or its carrier substance water (5 times weekly, 6weeks) are depicted. Medians with quartiles are displayed. (B) Corresponding to (A), the data were plotted as growth curves. (C) The observed local tumour control rates (symbols) and calculated tumour control probabilities (TCP) after treatment with nelfinavir (80mg/kg body weight) or its carrier substance water and irradiation with 30 fractions within 6weeks are shown. The error bars represent the 95% confidence intervals of TCD50. Clinical and Translational Radiation Oncology 2017 2, 7-12DOI: (10.1016/j.ctro.2016.12.002) Copyright © 2016 The Authors Terms and Conditions