目的 研究姜黃素增強伊立替康對結(jié)腸癌SW620細胞的體外抑制作用,并探討其作用機制。方法 MTT法檢測不同質(zhì)量濃度伊立替康和姜黃素單用或聯(lián)合用藥對SW620細胞增殖的影響;流式細胞儀檢測不同質(zhì)量濃度伊立替康和姜黃素單用或聯(lián)合用藥對SW620細胞凋亡的影響,比較細胞凋亡率;采用蛋白質(zhì)印記法檢測不同質(zhì)量濃度伊立替康和姜黃素單用或聯(lián)合用藥對SW620細胞內(nèi)拓撲異構(gòu)酶I蛋白表達水平的影響。結(jié)果 伊立替康和姜黃素單用均對SW620細胞增殖具有抑制作用,呈濃度和時間相關(guān)性。5、50 μg/mL伊立替康分別與0~30 μg/mL姜黃素聯(lián)合處理SW620細胞12、24、48 h均具有協(xié)同抑制細胞活性的作用,且呈濃度和時間相關(guān)性。高質(zhì)量濃度比低質(zhì)量濃度的伊立替康與姜黃素聯(lián)合用藥抑制效果顯著(P<0.01)。0、20 μg/mL姜黃素分別與0、5、50 μg/mL伊立替康聯(lián)合處理SW620細胞12、24、48 h,姜黃素可以增強伊立替康誘導(dǎo)的SW620細胞凋亡率。20 μg/mL姜黃素聯(lián)合5、50μg/mL伊立替康顯著上調(diào)了SW620細胞內(nèi)拓撲異構(gòu)酶-Ⅰ蛋白的表達,協(xié)同誘導(dǎo)了SW620細胞內(nèi)拓撲異構(gòu)酶-Ⅰ蛋白的表達。結(jié)論 伊立替康聯(lián)合姜黃素可以協(xié)同增強對SW620細胞活性的抑制作用,協(xié)同誘導(dǎo)SW620細胞凋亡,其作用機制可能與伊立替康、姜黃素上調(diào)拓撲異構(gòu)酶-Ⅰ表達有關(guān)。

ObjectiveTo investigate inhibitory effect of curcumin combined with irinotecan growth of colon cancer SW620 cells and explore its mechanism. Methods After treated by various concentrations of curcumin and irinotecan alone or both, the cell proliferations of SW620 cell were detected by MTT assay. Effect of various concentrations of curcumin combined with irinotecan or alone on apoptosis of SW620 cell were studied by flow cytometry and apoptosis rates were compared. The topoisomerase I protein expression levels in the cell were analyzed by Western blotting method. Results Curcumin or irinotecan had inhibition on cell proliferation by concentration- and time-dependent manners. There were synergistic inhibitions against SW620 cell viability treated by 5 and 50 μg/mL curcumin combined with 0 - 30 μg/mL irinotecan for 12, 24, and 48 h in concentration and time dependent manner. There were significant differences between high and low concentrations of irinotecan combined with curcumin (P < 0.01). After treated by 0 and 20 μg/mL curcumin combined with 0, 5, and 50 μg/mL irinotecan on SW620 cells for 12, 24, and 48 h, curcumin could enhance SW620 cell apoptosis rates induced by irinotecan. Curcumin (20 μg/mL) combined with 5 and 50 μg/mL irinotecan could significantly up-regulate the expression of topoisomerase I protein in SW620 cells, and synergetically induce the expression of topoisomerase I protein. Conclusions Irinotecan combined with curcumin can synergetically enhance inhibition against colon cancer SW620 cells, induce SW620 cell apoptosis, which may be related to up-regulation of the expression of topoisomerase I protein in SW620 cells by irinotecan and curcumin.

天津市衛(wèi)生局科技基金項目(2012KY20)