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目的:探讨蛋白酪氨酸磷酸酶(PTEN)蛋白表达对酪氨酸激酶抑制剂(TKI)耐药性的影响。方法:采用H-157和H-1355肺癌细胞体外培养,两种细胞均分为空白对照组和酪氨酸激酶抑制剂处理组。应用细胞生长曲线评价酪氨酸激酶抑制剂对细胞的抑制作用;应用流式细胞术检测细胞凋亡和周期;应用蛋白质印迹法测定细胞表皮生长因子受体(EGFR)和PTEN蛋白表达并评价PTEN表达对TKI疗效的影响。结果:H-157和H-1355两种肺癌细胞均呈现EGFR高表达,但H-1355细胞PTEN蛋白呈现高表达,而H-157细胞PTEN表达很低。应用TKI处理后,H-157细胞生长未见明显抑制,t=1.13,P>0.05;而H-1355细胞生长曲线下移明显,t=7.95,P<0.05。流式细胞仪检测显示,H-1355细胞TKI处理后导致(11.74±1.93)%的凋亡率(q=14.26,P<0.01)以及(83.74±3.93)%的G1期阻滞(q=9.54,P<0.01),而H-157细胞凋亡和G1期阻滞的百分率分别为(3.18±0.61)%(q=2.11,P>0.05)和(63.65±4.61)%(q=1.75,P>0.05)。结论:PTEN基因是TKI对肿瘤细胞抑制作用的重要调节因子,PTEN低表达导致肿瘤细胞对TKI原发耐药。
Objective: To investigate the effect of protein tyrosine phosphatase (PTEN) protein expression on tyrosine kinase inhibitor (TKI) resistance. Methods: H-157 and H-1355 lung cancer cells were cultured in vitro. Both cells were divided into blank control group and tyrosine kinase inhibitor treatment group. The cell growth curve was used to evaluate the inhibitory effect of tyrosine kinase inhibitor on cells. Flow cytometry was used to detect the apoptosis and cell cycle. The expressions of EGFR and PTEN protein were detected by Western blotting and PTEN Effect of expression on the efficacy of TKI. RESULTS: Both H-157 and H-1355 lung cancer cells showed high EGFR expression, but H-157 cells showed high expression of PTEN protein and low expression of PTEN in H-157 cells. The growth of H-157 cells was not significantly inhibited by TKI treatment, t = 1.13, P> 0.05; however, the growth curve of H-1355 cells shifted down significantly, t = 7.95, P <0.05. Flow cytometry showed that the apoptosis rate of H-1355 cells treated with TKI was (11.74 ± 1.93)% (q = 14.26, P <0.01) and (83.74 ± 3.93)% , P <0.01). The percentages of apoptosis and G1 arrest in H-157 cells were (3.18 ± 0.61)% (q = 2.11, P> 0.05) and (63.65 ± 4.61)% > 0.05). Conclusion: The PTEN gene is an important regulator of tumor cell inhibition by TKI. Low expression of PTEN leads to tumor cells primary resistance to TKI.