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Fig. 7 | Journal of Experimental & Clinical Cancer Research

Fig. 7

From: Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition

Fig. 7

Valproic acid/simvastatin combination potentiates docetaxel antitumor effect and reverts docetaxel-resistance in vivo in prostate cancer xenograft models. a 22Rv1 and b DU145R80 cells (5 × 106), were s.c. injected into athymic mice as described in the Methods section. When established tumors were palpable, mice were treated with vehicles or VPA (200 mg/kg i.p.) and SIM (2 mg/Kg i.p.) combination every day for two weeks, DTX (10 mg/Kg i.p.), once a week, or triple VPA/SIM/DTX combination. Relative tumor volume curves for 22Rv1 (left panel) and DU145R80 (right panel) xenografts. Means ± SD tumour volume measured at pre-specified time points. Inset, body weight measured two times/week. c Expression of cleaved PARP, γH2AX, AcH3, HMGCR and pYAP protein expression from xenograft 22Rv1 tumor samples evaluated by western blot (abbreviation = V + S: VPA + SIM; V + S + D: VPA + SIM + DTX); ponceau red was used as loading control. d BIRC5 (left panel) and NANOg (right panel) mRNA expression determined by RT-PCR in 22Rv1 samples. β-actin was used as housekeeping control gene to normalize RT-PCR reactions. Tukey’s multiple comparisons test, demonstrated statistically significant diffrences for VPA/SIM and VPA/SIM/DTX groups versus CTR and DTX groups. e Cholesterol content measured by NMR spectroscopy in tumor samples from untreated or 22Rv1-treated xenografts as indicated. The box and whisker plots summarize the normalized values of the proton signals of the cholesterol at 0.66 ppm for all samples. f 22Rv1 R_39 cells (6 × 106) were s.c. injected into athymic mice as described in the Methods section. When established tumors were palpable, mice were treated with vehicles or VPA and/or SIM every day for two weeks, and or DTX once a week, or triple VPA/SIM/DTX combination at the dosages indicated above for 22Rv1 parental cells xenograft model. Means ± SD tumor volume measured at pre-specified time points. Inset, body weight measured two times/week. g Ex vivo volume (left panel) and weight (right panel) of tumors collected at the end of the experiment (day 13). Statistically significant results are reported (*** indicates P < 0.0005, ** indicates P < 0.005 and * indicates P < 0.05)

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