Objective   To investigate the multi-drug resistance reversal effects of curcumin on xenografts derived from multi-drug resistant human colon

carcinoma cell line HCT-8/VCR

and to explore the possible mechanism.   Methods   The models of HCT-8/VCR xenograft (100 mm

3

) in nude mice were established through implanting 0.1 ml cells at 4×10

7

cells/ml. Twenty nude mice bearing HCT-8/VCR tumors were randomized into 4 groups according to different treatments

that is

group A: control group

group B: VCR group (2 mg/kg injected around the tumor mass

once per 2 d

for 7 times)

group C: curcumin group(50 mg/kg

injected around the tumor mass

once per 2 d

for 7 times)

group D: curcumin plus VCR group (as combined the treatment of groups B and C). Tumor volume was calculated with L×D

2

/2 which were measured once per 2 d

for 14 d. Tumor weight was measured and specimens were collected from the mice in each group in 2 weeks after the interventions. Morphology of xenografts were investigated by HE staining. The expressions of MDRl

P-glycoprotein(P-gp) and survivin were observed with reverse transcriptase PCR and Western blot assay respectively. Effects of curcumin on reversing multi-drug resistance of tumor in different treatments were evaluated.   Results   Curcumin plus VCR significantly inhibited the growth of xenografts

with the tumor weight of group D (0.42±0.23 g) significantly lower than those of the other 3 groups (group A 1.21±0.25 g

group B 1.13±0.27 g and group C 0.75±0.27 g

P0.05). RT-PCR and Western blotting results showed that the expressions of MDRl mRNA (0.39±0.11)

P-gp (0.34±0.07)

survivin mRNA (0.80±0.12) and protein (0.40±0.11) in group C and those of MDRl mRNA (0.18±0.05)

P-gp (0.15±0.02)

survivin mRNA (0.63±0.04) and protein (0.40±0.11) in group D were significantly lower than those in group A (MDRl mRNA 0.99±0.23

P-gp 0.71±0.23

survivin mRNA 1.19±0.32 and protein 0.88±0.15

P0.05)

indicating that curcumin down regulated these expressions. HE staining revealed that group C and D had more lymphocytic infiltration

more nuclear pyknosis

fewer mitotic figures

and more extensive necrosis when compar

ed to the other groups.   Conclusion   Curcumin has strong reversal effects on multidrug resistance in HCT-8/VCR cells through down-regulating mRNA and protein expressions of MDR1 and survivin.