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Fig. 4 | Cancer Cell International

Fig. 4

From: Vitamin E δ-tocotrienol sensitizes human pancreatic cancer cells to TRAIL-induced apoptosis through proteasome-mediated down-regulation of c-FLIPs

Fig. 4

The effects of TRAIL and VEDT on tumor volume. a Effect of TRAIL (20 µg/Kg intraperitoneally) on alternate days and VEDT (200 mg/kg, Orally) twice a day and combination of the two drugs for 4 weeks on MiaPaPa-2 tumor volume in Athymic nude mice. The tumor volume significantly reduced in TRAIL and VEDT treated mice for 4 weeks compared to vehicle (cP < .001 and cP < .001). However the combination of the two drugs resulted in a more significant inhibition of tumor volume compared to vehicle (cP < .001) or either drug alone (dP < .02). b Effect of TRAIL (20 µg/Kg intraperitoneally) on alternate days and VEDT (200 mg/kg, Orally) twice a day and combination of the two drugs for 4 weeks on MiaPaPa-2 tumor weight in athymic nude mice. The tumor weights were significantly reduced in TRAIL and VEDT (aP < .02) treated mice for 4 weeks compared to vehicle (aP < .02 and a0P < .02). However, the combination of the two drugs resulted in a more significant inhibition of tumor weight compared to vehicle (bP < .01) or either drug alone (cP < .05). c Western blot analyses of cleaved caspase-8, cleaved caspase-3, cleaved PARP, and c-FLIPs in tumor tissues following treatment with TRAIL alone or in combination with VEDT for 4 weeks (n = 5). β-Actin served as loading control. TRAIL and VEDT alone induced apoptosis (elevated cleaved caspase-8, cleaved caspase-3, and cleaved PARP). Greater induction of apoptosis was noted in tumor tissues following combined drug treatment than with either drug alone. VEDT alone and in combination with TRAIL but not TRAIL alone depleted tumor tissue c-FLIPs expression. d Histological data depicting the Ki-67, cleaved caspase-3, and cleaved caspase-8 in tumor tissues following treatment with TRAIL (T) alone or in combination with VEDT (DT3) for 4 weeks (n = 5). e Greater and significant induction of apoptosis (cleaved caspase-8, bP < .001) and inhibition of tumor cell proliferation (Ki-67, bP < .001) was noted in tumor tissues following combined drug treatment than with either drug alone. VEDT alone significantly induced cleaved caspase 3 compared to vehicle (bP < .001) and was greater than TRAIL-alone treatment (cP < .001). The combination significantly induced cleaved caspase 3 compared to vehicle (aP < .01) and compared to TRAIL alone (dP < .05)

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