CXCR4抑制剂AMD3465调节肺癌细胞株增殖、侵袭的实验研究

doi:10.3877/cma.j.issn.1674-6902.2017.04.004

目的

探讨CXCR4抑制剂AMD3465对肺癌细胞株增殖、侵袭的影响。

方法

培养肺癌细胞株A549并分为AMD3465组、对照组；分别用含有三种不同剂量(50 、100、200 mg/L)AMD3465的DMEM处理以及用不含药物的DMEM处理。处理后12、24、48 h，检测细胞的增殖活力和侵袭数目；处理后48 h，检测细胞中增殖及侵袭基因的mRNA表达量。

结果

处理后12、24、48 h，三种不同剂量(50、100、200 mg/L)AMD3465组细胞的OD值均显著低于对照组、侵袭数目均显著少于对照组，AMD3456剂量较低时OD值、侵袭数目与对照组差距均大于AMD3456剂量较高时(P<0.05)；处理后48 h，50 mg/L AMD3465组、100 mg/L AMD3465组、200 mg/L AMD3465组细胞中CyclinD1、PCNA、Ki-67、CatB、MMP2、MMP9、MMP13的mRNA表达量均显著低于对照组；AMD3456剂量较低时细胞中CyclinD1、PCNA、Ki-67、CatB、MMP2、MMP9、MMP13的mRNA表达量与对照组差距均大于AMD3456剂量较高时(P<0.05)。

结论

CXCR4抑制剂AMD3465能够有效抑制肺癌细胞株的增殖、侵袭。

关键词: 支气管肺癌, CXC受体4, 增殖, 侵袭

Objective

To study the effect of CXCR4 inhibitor AMD3465 on proliferation and invasion of lung carcinoma cell lines.

Methods

The lung carcinoma cell line A549 was cultured and divided into 50 mg/L AMD3465 group, 100 mg/L AMD3465 group, 200 mg/L AMD3465 group treated with DMEM containing different dosage of AMD3465 and control group treated DMEM without drug. After 12 h, 24 h and 48 h, the proliferation and invasion number of the cells were detected. After 12 h, the mRNA expression of cell proliferation and invasion genes were detected.

Results

12 h, 24 h, 48 h after treatment, OD values of 50 mg/L AMD3465 group, 100 mg/L AMD3465 group, 200 mg/L AMD3465 group were significantly lower than the control group, invasion number were significantly less than the control group, the differences of OD values and invasion number between control group and lower dosage ADM3456 group were larger than higher dosage AMD3465(P<0.05); 48 hours after treatment, mRNA expression of CyclinD1, PCNA, Ki-67 cells, CatB, MMP2, MMP9, MMP13 of 50mg/L AMD3465 group, 100 mg/L AMD3465 group, 200 mg/L AMD3465 group were significantly lower than the control group; the differences of mRNA expression of CyclinD1, PCNA, Ki-67 cells, CatB, MMP2, MMP9, MMP13 between control group and lower dosage ADM3456 group were larger than higher dosage AMD3465(P<0.05).

Conclusion

CXCR4 inhibitor AMD3465 can effectively inhibit the proliferation and invasion of lung carcinoma cell lines.

Key words: Bronchogenic carcinoma, CXC receptor 4, Proliferation, Invasion

表1 两组细胞的增殖活力比较

剂量及组别		例数	12 h	24 h	48 h
50 mg/L AMD3465组		5	0.312±0.055^a	0.289±0.036^a	0.336±0.049^a
100 mg/L AMD3465组		5	0.398±0.064^ab	0.447±0.081^ab	0.483±0.068^ab
200 mg/L AMD3465组		5	0.452±0.077^abc	0.502±0.089^abc	0.593±0.077^abc
?	对照组	5	0.523±0.078	0.641±0.089	0.702±0.093

表1 两组细胞的增殖活力比较

剂量及组别		例数	12 h	24 h	48 h
50 mg/L AMD3465组		5	0.312±0.055^a	0.289±0.036^a	0.336±0.049^a
100 mg/L AMD3465组		5	0.398±0.064^ab	0.447±0.081^ab	0.483±0.068^ab
200 mg/L AMD3465组		5	0.452±0.077^abc	0.502±0.089^abc	0.593±0.077^abc
?	对照组	5	0.523±0.078	0.641±0.089	0.702±0.093

表2 两组细胞的侵袭能力比较

剂量及组别		例数	12 h	24 h	48 h
50 mg/L AMD3465组		5	78.49±9.32^a	80.24±9.31^a	83.19±9.72^a
100 mg/L AMD3465组		5	103.22±16.58^ab	114.58±12.39^ab	123.15±14.58^ab
200 mg/L AMD3465组		5	128.65±16.84^abc	145.24±19.74^abc	189.32±22.36^abc
?	对照组	5	156.22±22.31	195.62±25.27	247.58±31.28

表2 两组细胞的侵袭能力比较

剂量及组别		例数	12 h	24 h	48 h
50 mg/L AMD3465组		5	78.49±9.32^a	80.24±9.31^a	83.19±9.72^a
100 mg/L AMD3465组		5	103.22±16.58^ab	114.58±12.39^ab	123.15±14.58^ab
200 mg/L AMD3465组		5	128.65±16.84^abc	145.24±19.74^abc	189.32±22.36^abc
?	对照组	5	156.22±22.31	195.62±25.27	247.58±31.28

表3 两组细胞中增殖基因的表达量比较

剂量及组别		例数	CyclinD1	PCNA	Ki-67
50 mg/L AMD3465组		5	0.35±0.07^a	0.42±0.08^a	0.29±0.04^a
100 mg/L AMD3465组		5	0.57±0.08^ab	0.64±0.09^ab	0.52±0.07^ab
200 mg/L AMD3465组		5	0.82±0.09^abc	0.78±0.06^abc	0.85±0.11^abc
?	对照组	5	1.07±0.14	0.95±0.11	1.10±0.18

表3 两组细胞中增殖基因的表达量比较

剂量及组别		例数	CyclinD1	PCNA	Ki-67
50 mg/L AMD3465组		5	0.35±0.07^a	0.42±0.08^a	0.29±0.04^a
100 mg/L AMD3465组		5	0.57±0.08^ab	0.64±0.09^ab	0.52±0.07^ab
200 mg/L AMD3465组		5	0.82±0.09^abc	0.78±0.06^abc	0.85±0.11^abc
?	对照组	5	1.07±0.14	0.95±0.11	1.10±0.18

表4 两组细胞中侵袭基因的表达量比较

剂量及组别	例数	CatB	MMP2	MMP9	MMP13
50 mg/L AMD3465组	5	0.42±0.08^a	0.33±0.06^a	0.56±0.09^a	0.38±0.07^a
100 mg/L AMD3465组	5	0.64±0.08^ab	0.50±0.07^ab	0.72±0.09^ab	0.51±0.08^ab
200 mg/L AMD3465组	5	0.80±0.11^abc	0.77±0.09^abc	0.85±0.12^abc	0.78±0.04^abc
对照组	5	1.15±0.18	1.05±0.17	1.08±0.14	0.98±0.11

表4 两组细胞中侵袭基因的表达量比较

剂量及组别	例数	CatB	MMP2	MMP9	MMP13
50 mg/L AMD3465组	5	0.42±0.08^a	0.33±0.06^a	0.56±0.09^a	0.38±0.07^a
100 mg/L AMD3465组	5	0.64±0.08^ab	0.50±0.07^ab	0.72±0.09^ab	0.51±0.08^ab
200 mg/L AMD3465组	5	0.80±0.11^abc	0.77±0.09^abc	0.85±0.12^abc	0.78±0.04^abc
对照组	5	1.15±0.18	1.05±0.17	1.08±0.14	0.98±0.11

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Experimental study of CXCR4 inhibitor AMD3465 regulating proliferation and invasion of lung carcinoma cell line

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Experimental study of CXCR4 inhibitor AMD3465 regulating proliferation and invasion of lung carcinoma cell line