基于HER2/PI3K/Akt通路的脂肪酸合酶对大肠癌细胞生物学行为及耐药性的影响

Study on effect of fatty acid synthase on biological behaviors and drug resistance of colorectal cancer cells based on HER2/PI3K/Akt pathway

目的探讨脂肪酸合酶通过人表皮生长因子受体-2(HER2)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)轴对大肠癌细胞生物学行为及耐药性的影响。方法选取2017年1月至2019年1月该院收治的31例大肠癌患者癌组织及癌旁组织,比较癌组织和癌旁组织脂肪酸合酶(FAS)及HER2 mRNA水平。选取大肠癌细胞株LOVO及正常人肠上皮细胞HIEC细胞系进行体外实验,采用Western blot法检测细胞株FAS及HER2蛋白相对表达量。向LOVO细胞株分别转染Si-FAS和阴性对照(Si-NC)24 h,随后检测HER2、PI3K及Akt蛋白相对表达量,并检测细胞增殖、凋亡、迁徙及侵袭情况。转染24 h后,加入不同浓度(0、0.465、3.720、29.800、238.000、1904.000μmol/L)奥沙利铂,加药48 h后检测细胞活性。结果相较于癌旁组织及HIEC细胞株,大肠癌组织及LOVO细胞株FAS、HER2 mRNA水平更高(P<0.05)。相较于Si-NC组,Si-FAS组HER2、PI3K及Akt蛋白水平均有所下降,且细胞迁徙及侵袭能力减弱,细胞凋亡率有所上升,而细胞增殖抑制率随时间增加而上升(P<0.05)。加入奥沙利铂48 h后,NC组及Si-FAS组细胞活性随药物浓度有所降低,且Si-FAS组降低程度比Si-NC组大(P<0.05)。结论脂肪酸合酶参与肠癌化疗药物的耐药机制,并可能通过HER2/PI3K/Akt信号通路参与大肠癌细胞的生物学行为。

Objective To investigate the effect of fatty acid synthase(FAS)on the biological behaviors and drug resistance of intestinal cancer cells through the HER2/PI3K/Akt axis.Methods The cancer tissues and paracancerous tissues of 31 patients with colorectal cancer treated in this hospital were selected for comparing the levels of FAS and HER2 mRNA between cancer tissues and paracancerous tissues.The colorectal cancer cell line LOVO and the normal human intestinal epithelial cell HIEC cell line were selected for conducting the in vitro experiments,and the relative expression levels of FAS and HER2 protein were detected by adopting the Western blot method.Si-FAS and the ngative control(Si-NC)were transfected into the LOVO cell line for 24 h,then the relative expression levels of HER2,PI3K and Akt protein were detected,and the cell proliferation,apoptosis,migration and invasion were detected.At 24 h after transfection,different concentrations of oxaliplatin(0,0.465,3.72,29.8,238,1904μmol/L)were added,and the cell viability was detected at 48 h after adding drug.Results Compared with paracancerous tissues and HIEC cell line,colorectal cancer tissues and LOVO cell line FAS and HER2 mRNA levels were higher(P<0.05).Compared with the Si-NC group,the levels of HER2,PI3K,and Akt protein in the Si-FAS group were decreased,moreover the cell migration and invasion ability were weakened,the cellular apoptosis rate was increased,and the cell proliferation inhibition rate was increased with time increase(P<0.05).At 48 h after adding oxaliplatin,the cell activity of the NC group and the Si-FAS group was decreased with the drug concentration,moreover the reduction degree ofthe Si-FAS group was greater than that of the NC group(P<0.05).Conclusion Fatty acid synthase is involved in the drug resistance mechanism of colorectal cancer chemotherapy drugs,moreover may participate in the biological behaviors of colorectal cancer cells through the HER2/PI3K/Akt signaling pathway.