ABCG2介导的多耐药在小细胞肺癌中的作用
|
摘要
目的:筛选小细胞肺癌(SCLC)耐药相关的基因,为逆转SCLC多耐药寻找理想靶标。方法:镜下观察H69与H69AR细胞形态,CCK8分析不同浓度顺铂和依托泊苷对H69和H69AR药物抑制率,使用QRT-PCR,Western blot检测H69AR相对H69细胞ABCG2表达情况,QRT-PCR分析ABCG2在10例行化疗与产生耐药时SCLC患者血液标本中的表达情况。结果:H69AR细胞ABCG2蛋白表达量显著高于H69 (P<0.05), SCLC患者耐药时ABCG2表达水平显著高于化疗前(P<0.01)。结论:ABCG2基因可能作为逆转SCLC多耐药的理想靶点。
Objective:To screen the drug resistance-related genes in small cell lung cancer(SCLC), and to find an ideal target for reversing multidrug resistance in SCLC.Methods:The morphology of H69 and H69 AR cells was observed under microscope. CCK8 was used to analyze the inhibition rates of cisplatin and etoposide at different concentrations on H69 and H69 AR. QRT-PCR and Western blot were used to detect the expression of ABCG2 in H69 AR cells. QRT-PCR was used to analyze the expression of ABCG2 in blood samples of 10 SCLC patients before chemotherapy and when they developed drug resistance.Results:The expression of ABCG2 in H69 AR cells was significantly higher than that in H69 cells(P<0.05). The expression of ABCG2 in 10 SCLC patients when they developed drug resistance was significantly higher than that before chemotherapy(P<0.01).Conclusion:ABCG2 gene may be an ideal target for reversing multidrug resistance in SCLC.
Objective:To screen the drug resistance-related genes in small cell lung cancer(SCLC), and to find an ideal target for reversing multidrug resistance in SCLC.Methods:The morphology of H69 and H69 AR cells was observed under microscope. CCK8 was used to analyze the inhibition rates of cisplatin and etoposide at different concentrations on H69 and H69 AR. QRT-PCR and Western blot were used to detect the expression of ABCG2 in H69 AR cells. QRT-PCR was used to analyze the expression of ABCG2 in blood samples of 10 SCLC patients before chemotherapy and when they developed drug resistance.Results:The expression of ABCG2 in H69 AR cells was significantly higher than that in H69 cells(P<0.05). The expression of ABCG2 in 10 SCLC patients when they developed drug resistance was significantly higher than that before chemotherapy(P<0.01).Conclusion:ABCG2 gene may be an ideal target for reversing multidrug resistance in SCLC.
引文
[1]朱代峰,桂淑玉. 非小细胞肺癌的治疗进展[J]. 临床肺科杂志, 2010,15(3):372-374.
[2]张宇飞,郭丽,赵峰,等.ABCG2在肺癌中的表达及意义[J].解放军医学杂志,2007,32(9):965-967.
[3]DOYLE L A, YANG W, ABRUZZO L V, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells[J]. Proceedings of the National Academy of Sciences of the United States of America, 1998, 95(26): 15665-15670.
[4]WANG B,YANG H,HUANG Y Z, et al. Biologic characteristics of the side population of human small cell lung cancer cell line H446[J]. Chin J Cancer,2010,29(3): 254-260.
[5]VESEL M, RAPP J, FELLER D, et al.ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling[J]. Respiratory research,2017, 18(1):52.
[6]KIM Y H, ISHII G, GOTO K, et al. Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer[J]. Lung Cancer, 2009, 65(1): 105-111.
[7]MUELLER P J, DALLY H, KLAPPENECKER C N, et al. Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer patients[J]. International Journal of Cancer, 2009, 124(7): 1669-1674.
[8]ZHANG G H, ZHANG Y K, WANG Y J, et al. Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: in vitro and in vivo[J]. Cancer Letters, 2018, 424(424): 19-29.
[9]MINAMI T,KIJIMA T, OTANI Y,et al.HER2 as therapeutic target for overcoming ATP-binding cassette transporter-mediated chemoresistance in small cell lung cancer[J].Mol Cancer Ther,2012,11(4):830-841.
[2]张宇飞,郭丽,赵峰,等.ABCG2在肺癌中的表达及意义[J].解放军医学杂志,2007,32(9):965-967.
[3]DOYLE L A, YANG W, ABRUZZO L V, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells[J]. Proceedings of the National Academy of Sciences of the United States of America, 1998, 95(26): 15665-15670.
[4]WANG B,YANG H,HUANG Y Z, et al. Biologic characteristics of the side population of human small cell lung cancer cell line H446[J]. Chin J Cancer,2010,29(3): 254-260.
[5]VESEL M, RAPP J, FELLER D, et al.ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling[J]. Respiratory research,2017, 18(1):52.
[6]KIM Y H, ISHII G, GOTO K, et al. Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer[J]. Lung Cancer, 2009, 65(1): 105-111.
[7]MUELLER P J, DALLY H, KLAPPENECKER C N, et al. Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer patients[J]. International Journal of Cancer, 2009, 124(7): 1669-1674.
[8]ZHANG G H, ZHANG Y K, WANG Y J, et al. Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: in vitro and in vivo[J]. Cancer Letters, 2018, 424(424): 19-29.
[9]MINAMI T,KIJIMA T, OTANI Y,et al.HER2 as therapeutic target for overcoming ATP-binding cassette transporter-mediated chemoresistance in small cell lung cancer[J].Mol Cancer Ther,2012,11(4):830-841.