AIM： To investigate the ability of hexahydrocurcumin （HHC） to enhance 5-fluorouracil （5-FU） in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase （COX）-2 expression.METHODS： Antiproliferative e...AIM： To investigate the ability of hexahydrocurcumin （HHC） to enhance 5-fluorouracil （5-FU） in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase （COX）-2 expression.METHODS： Antiproliferative effects of HHC and 5-FU, alone and in combination, on growth of HT-29 human colon cancer cells were assessed using 5-diphenyltetrazolium bromide （MTT） reduction assay. In combinationtreatment, low doses of 5-FU were used combined with various concentrations of HHC to minimize the toxic- ity and side effects of 5-FU. The therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein expression were examined using semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting analysis.RESULTS： Ml-I- reduction assay indicated that HHC alone markedly decreased the viability of HT-29 human colon cancer cells compared to control. Semi-quantitative RT-PCR analysis indicated that HHC is a selective COX-2 inhibitor. This finding was supported by the ob- servation that HHC significantly down-regulates COX-2 mRNA expression compared to the control （control： 100.05% ± 0.03% vs HHC： 61.01% ± 0.35%, P 〈 0.05） but does not alter COX-1 mRNA. In combined treatment, addition of HHC to a low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by markedly reducing cell viability to a greater degree than monotherapy. Semi-quantitative RT-PCR indicated that 5-FU at the concentration of 5 pmol/L in combina- tion with HHC at the concentration of 25 pmol/L signifi- cantly down-regulates COX-2 mRNA expression when compared with values in cells treated with 5-FU or HHC alone （HHC ＋ 5-FU： 31.93% ± 5.69%, 5-FU： 100.66% ± 4.52% vs HHC： 61.01% ±0.35%, P 〈 0.05）.CONCLUSION： HHC together with 5-FU exerts a synergistic effect and may prove chemotherapeutically useful in treating human colon cancer.展开更多
基金Supported by National Research Council of ThailandPartial support from The Strategic Basic Research Grant of The Thailand Research Fund
文摘AIM： To investigate the ability of hexahydrocurcumin （HHC） to enhance 5-fluorouracil （5-FU） in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase （COX）-2 expression.METHODS： Antiproliferative effects of HHC and 5-FU, alone and in combination, on growth of HT-29 human colon cancer cells were assessed using 5-diphenyltetrazolium bromide （MTT） reduction assay. In combinationtreatment, low doses of 5-FU were used combined with various concentrations of HHC to minimize the toxic- ity and side effects of 5-FU. The therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein expression were examined using semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting analysis.RESULTS： Ml-I- reduction assay indicated that HHC alone markedly decreased the viability of HT-29 human colon cancer cells compared to control. Semi-quantitative RT-PCR analysis indicated that HHC is a selective COX-2 inhibitor. This finding was supported by the ob- servation that HHC significantly down-regulates COX-2 mRNA expression compared to the control （control： 100.05% ± 0.03% vs HHC： 61.01% ± 0.35%, P 〈 0.05） but does not alter COX-1 mRNA. In combined treatment, addition of HHC to a low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by markedly reducing cell viability to a greater degree than monotherapy. Semi-quantitative RT-PCR indicated that 5-FU at the concentration of 5 pmol/L in combina- tion with HHC at the concentration of 25 pmol/L signifi- cantly down-regulates COX-2 mRNA expression when compared with values in cells treated with 5-FU or HHC alone （HHC ＋ 5-FU： 31.93% ± 5.69%, 5-FU： 100.66% ± 4.52% vs HHC： 61.01% ±0.35%, P 〈 0.05）.CONCLUSION： HHC together with 5-FU exerts a synergistic effect and may prove chemotherapeutically useful in treating human colon cancer.
