魔芋葡甘露聚糖逆转大肠癌5-氟尿嘧啶耐药的作用及其机制研究

目的 探究魔芋葡甘露聚糖（konjac glucomannan，KGM）体内外逆转大肠癌5-氟尿嘧啶（5-fluorouracil， 5-FU）耐药作用及其相关机制。方法 构建HCT-8/5-FU耐药细胞株，采用MTT法验证HCT-8/5-FU细胞的耐药性以及KGM和5-FU对HCT-8/5-FU细胞的增殖抑制作用；采用CompuSyn软件分析KGM和5-FU联合用药的联合指数，评价联合效应；流式细胞术检测两药对HCT-8/5-FU细胞凋亡的影响；Western blotting检测PI3K/Akt信号通路蛋白表达情况；构建裸鼠移植瘤模型，检测KGM和5-FU体内抑瘤效果。结果 HCT-8/5-FU细胞株对5-FU的敏感性显著降低；KGM和5-FU单用均能够抑制HCT-8/5-FU细胞的增殖，两者联用能够更加有效地抑制HCT-8/5-FU细胞增殖；CompuSyn软件分析结果表明KGM和5-FU具有协同作用；KGM和5-FU联用能够显著增加HCT-8/5-FU细胞凋亡率，并抑制PI3K/Akt信号通路活性（P<0.05）；KGM和5-FU联用的抑瘤率显著高于5-FU单独使用（P<0.05）。结论 KGM能够逆转大肠癌5-FU耐药，其作用机制跟PI3K/Akt信号通路有关。

Study on Effect and Its Mechanism of Konjac Glucomannan on the Reversal of 5-Fluorotracicl Resistance in Colorectal Cancer

OBJECTIVE To investigate the reversal effect of 5-fluorouracil(5-FU) resistance of colorectal cancer by konjac glucomannan(KGM) in vivo and in vitro and its related mechanism.METHODS HCT-8/5-FU resistant cell lines were constructed, and MTT assay was used to verify the resistance of HCT-8/5-FU cells and the inhibitory effect of KGM and 5-FU on proliferation of HCT-8/5-FU cells.The combined index of KGM and 5-FU was analyzed by CompuSyn software to evaluate the combined effect.The effects of the two drugs on apoptosis were detected by flow cytometry.Expression of PI3K/Akt signaling pathway was detected by Western blotting.The transplanted tumor model of nude mice was constructed to detect the tumor inhibition effect of KGM and 5-FU in vivo.RESULTS The sensitivity of HCT-8/5-FU cell line to 5-FU was significantly decreased.Both KGM and 5-FU alone could inhibit the proliferation of HCT-8/5-FU cells, while the combination of the two could inhibit the proliferation of HCT-8/5-FU cells more effectively.CompuSyn software analysis results showed that KGM and 5-FU had a synergistic effect.KGM combined with 5-FU significantly increased the apoptosis rate of HCT-8/5-FU and inhibited the activity of PI3K/Akt signaling pathway (P<0.05).The tumor inhibition rate of KGM combined with 5-FU was significantly higher than that of 5-FU alone(P<0.05).CONCLUSION KGM can reverse 5-FU resistance in colorectal cancer, and its mechanism is related to the PI3K/Akt signaling pathway