Abstract
Objective To investigate the effect of curcumin (Cur) onresistance toirinotecan (CPT-11) inhuman colon carcinoma cells and explore the mechanism involved. Methods Drug-resistanthuman colon carcinoma cell line (LoVo/CPT-11) was established by exposure to gradually increased concentrationof CPT-11, cell counting kit-8 (CCK-8) assay was applied to detect the growth inhibition rate and figure up the resistance index. Western blotting was used to examine the change of cancer stem cell (CSC) markers CD44 and CD133. The effect of Cur on resistance to CPT-11 was detected after treatment with the mixture of Cur (5, 10, 20 μmol/L) and CPT-11. Additionally, drug-resistant cells were separatedinto four groups: the control group, the Cur group, the CPT-11 group and the mixture group. The protein expression levels of CSC markers and the proportion of CD133+ cellswere detectedinthe four groups. Results The resistance index of LoVo/CPT-11 cell was 6.21 and itsprotein expression levels of CD44 and CD133 weresignificantly higher than LoVo cell (1.63±0.42 vs. 0.59±0.07, 0.75±0.13 vs. 0.24±0.02; P=0.023, 0.019). The 50% inhibition dose (IC50)of CPT-11 in LoVo/CPT-11 cellstreated with Cur (5, 10, 20 μmol/L) and CPT-11 was (144.48±3.22), (100.72±2.08), (146.87±2.73) μmol/L respectively, there wassignificant decrease compared with the control group [(268.72±2.43) μmol/L, P=0.031, 0.020, 0.036]. The protein expression levels of CD44 and CD133 in the Cur group and the mixture group were significantly decreased compared with the CPT-11 group (2.11±0.45, 1.79±0.55 vs. 3.04±0.64; P=0.041, 0.034; 1.34±0.13, 0.52±0.04 vs. 1.60±0.15; P=0.044, 0.020), and the proportion of CD133+ cells wasalso significantly lower than the CPT-11 group[(2.91±0.29)%, (1.11±0.14)% vs. (3.53±0.37)%; P=0.028, 0.016]. Conclusion CSC was related to the acquired chemoresistance of human colon carcinoma cells, Cur could reduce chemoresistance in human colon carcinoma cells by inhibiting the characterization of CSC. Key words: Curcumin; Irinotecan; Colon carcinoma; Chemoresistance; Cancer stem cells
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