马蔺子素联合化疗药对肿瘤细胞增殖和凋亡的影响

Effects of irisquinone combined with chemotherapeutic drugs on proliferation and apoptosis of tumor cells

目的研究马蔺子素联合化疗药对肿瘤细胞增殖和凋亡的影响。方法采用MTT法测定马蔺子素及其联合顺铂、多柔比星、5-氟尿嘧啶对人肝癌细胞SMMC-7721、人结肠癌细胞LOVO、人肺癌细胞A549、人胃癌细胞BGC-823和人乳腺癌细胞MCF-7的抑制作用。流式细胞仪检测马蔺子素(0.5μg/mL)组、顺铂(5μg/m L)组、多柔比星(0.5μg/mL)组、5-氟尿嘧啶(500μg/mL)组、联合用药组(0.5μg/mL马蔺子素+5μg/mL顺铂组、0.5μg/mL马蔺子素+0.5μg/mL多柔比星组、0.5μg/mL马蔺子素+500μg/mL 5-氟尿嘧啶组)对A549细胞凋亡和周期变化情况的影响。结果马蔺子素对肿瘤细胞的生长具有明显的抑制作用,IC_(50)值分别为10.43、1.94、8.73、3.37、4.89μg/mL。马蔺子素与顺铂、多柔比星、5-氟尿嘧啶联合作用后,均能明显增加后者对A549细胞增殖的抑制作用,二者有明显的协同作用。单用5-氟尿嘧啶、顺铂和多柔比星,A549细胞比例分别在G_0/G_1、S和G_2/M期均显著增加,且与马蔺子素合用后A549细胞比例在相应周期均显著增加(P<0.05)。合用组肿瘤细胞凋亡率也显著升高(P<0.05)。与对照组比较,顺铂、多柔比星和5-氟尿嘧啶单用及与马蔺子素合用均可显著升高细胞的凋亡率(P<0.05),且马蔺子素与顺铂或多柔比星联合用药时,细胞凋亡率显著高于单独使用相应的化疗药(P<0.05)。结论马蔺子素联合化疗药能明显抑制肿瘤细胞的增殖,其机制与影响细胞周期调控和诱导细胞凋亡有关。

Objective To investigate the influence of irisquinone combined with chemotherapeutic drugs on proliferation and apoptosis of tumor cells.Methods MTT assay was used to determine the inhibitory effect of irisquinone and its combination with cisplatin,doxorubicin,and 5-fluorouracil on SMMC-7721 cells,LOVO cells,A549 cells,BGC-823 cells,and MCF-7 cells.The effects of irisquinone(0.5μg/mL)group,cisplatin(5μg/m L)group,doxorubicin(0.5μg/mL)group,5-fluorouracil(500μg/mL)group,and combined medication group(irisquinone 0.5μg/mL+cisplatin 5μg/m L,irisquinone 0.5μg/m L+doxorubicin 0.5μg/m L,irisquinone 0.5μg/mL+5-fluorouracil 500μg/mL)on apoptosis and cycle changes of A549 cells were detected by flow cytometry.Results Irisquinone could significantly inhibit the growth of tumor cells with IC50 of 10.43,1.94,8.73,3.37,and 4.89μg/mL,respectively.The combination of irisquinone with cisplatin,doxorubicin,and 5-fluorouracil could significantly increase the inhibitory effect of the latter on the proliferation of A549 cells,and the synergistic effects of irisquin with cisplatin,doxorubicin,and 5-fluorouracil were obvious.When the 5-fluorouracil,cisplatin,and doxorubicin were used alone,the proportion of A549 cells was significantly increased in G0/G1,S,and G2/M phases,respectively,and the proportion of A549 cells was significantly increased in the corresponding cycles after the combination with irisquinone(P<0.05).Compared with the control group,cisplatin,doxorubicin,and5-fluorouracil used alone or combined with irisquinone were significantly increased the apoptotic rates(P<0.05),and the apoptotic rates of irisquinone combined with cisplatin or doxorubicin were significantly higher than those of chemotherapy alone.Conclusion Irisquinone combined with chemotherapeutic drugs can significantly inhibit the proliferation of tumor cells,and the mechanism is related to the influence of cell cycle regulation,and the induction of apoptosis.