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目的:探讨整合素β1表达上调对表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitor,EGFR-TKI)吉非替尼抑制非小细胞肺癌细胞增殖以及肿瘤生长的影响。方法:将PC9、PC9/PCD(脂质体pcDNA3.1稳定转染空白对照株)和PC9/D6(脂质体稳定转染整合素β1细胞株)3株细胞经0.5μmol/L吉非替尼作用后,MTT法检测3株细胞的增殖情况。建立3株细胞的裸鼠移植瘤模型,设治疗组(3mg/kg吉非替尼)和对照组(1%Tween-80),观察肿瘤的生长情况,绘制肿瘤生长曲线,称取瘤体质量,计算抑瘤率。免疫组织化学法检测裸鼠移植瘤组织中整合素β1、EGFR和pEGFR的表达情况。结果:转染了整合素β1的PC9/D6组增殖率明显高于PC9/PCD和PC9组(P<0.05)。吉非替尼对PC9/D6裸鼠移植瘤的生长抑制最不明显,抑制率是61.38%,与PC9/PCD和PC9组比较差异具有统计学意义(P<0.01);PC9/PCD和PC9组的抑制率分别是93.54%和95.16%。PC9/D6裸鼠移植瘤中整合素β1的表达水平高于PC9/PCD和PC9组(P<0.01)。EGFR在3组之间表达的差异无统计学意义。3组裸鼠移植瘤经吉非替尼治疗后,pEGFR表达水平均有不同程度的下降,但PC9/D6治疗组中pEGFR表达水平显著高于PC9/PCD和PC9组(P<0.01)。结论:无论体内或体外实验均显示,整合素β1表达上调可降低细胞株或移植瘤对吉非替尼的敏感性,提示整合素β1可能通过一种新的耐药机制参与了肿瘤细胞对EGFR-TKI的耐药。
Objective: To investigate the effects of up-regulation of integrin β1 on proliferation and tumor growth of non-small cell lung cancer cells by epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib. Methods: Three strains of PC9, PC9 / PCD (lipofectamine pcDNA3.1 stably transfected blank control strain) and PC9 / D6 (liposomal stably transfected integrin β1 cell strain) were treated with 0.5μmol / After the effect of Ni, the proliferation of 3 cells was detected by MTT assay. Three nude mice transplantation tumor models were established. The treatment group (3mg / kg gefitinib) and the control group (1% Tween-80) were established. The growth of the tumor was observed and the tumor growth curve was drawn. , Calculate the inhibition rate. Immunohistochemistry was used to detect the expression of integrin β1, EGFR and pEGFR in the transplanted tumor of nude mice. Results: The proliferation rate of PC9 / D6 transfected with integrin β1 was significantly higher than that of PC9 / PCD and PC9 groups (P <0.05). The inhibition rate of gefitinib on the growth of xenografts in PC9 / D6 nude mice was the least, the inhibition rate was 61.38%, which was significantly different from that in PC9 / PCD and PC9 groups (P <0.01) The inhibition rates were 93.54% and 95.16% respectively. The expression of integrin β1 in PC9 / D6 xenografts was higher than that in PC9 / PCD and PC9 groups (P <0.01). There was no significant difference in the expression of EGFR between the three groups. However, pEGFR expression in PC9 / D6-treated group was significantly higher than that in PC9 / PCD and PC9 groups (P <0.01). Conclusion: Both in vivo and in vitro experiments show that upregulation of integrin β1 can reduce the sensitivity of cell lines or xenografts to gefitinib, suggesting that integrin β1 may be involved in the tumor cell response to EGFR -TKI resistance.