iNOS抑制剂对鼻咽癌CNE-2细胞作用的探讨
摘要
目的:
观察诱导性一氧化氮合酶(iNOS)抑制剂SMT是否对鼻咽癌细胞株CNE-2有抑制细胞增殖能力和促进凋亡的能力,探讨SMT对顺铂的抗CNE-2细胞作用是否存在增敏效应及分子机制,为摸索治疗晚期鼻咽癌合理的药物组合提供实验依据。
方法:
1选用鼻咽癌细胞株CNE-2作为研究对象,以A549作为对照,RT-PCR测试CNE-2是否表达iNOS。
2用不同浓度的SMT、顺铂、二者合用作用于CNE-2细胞,干预CNE-2细胞后,MTT试验观察其对细胞活力的影响。
3 Hoechst33258染色观察细胞凋亡的形态学变化。
4流式细胞仪(FCM)检测细胞凋亡指数、凋亡的水平。
5硝酸还原酶法测NO的含量。
结果:
1.以iNOS高表达的肺癌细胞株A549为阳性对照,CNE-2细胞证实为iNOS阳性表达。
2.SMT以浓度依赖性方式有效地抑制CNE-2细胞增殖。
3.0.5umol/mL的SMT与6μg/ml的顺铂共同干预CNE-2细胞,较之单用SMT或顺铂抑制CNE-2细胞的凋亡形态学改变明显,凋亡小体以及核固缩现象增多。
4.0.5umol/mL的SMT与6μg/ml的顺铂共同干预CNE-2细胞,较之单用顺铂抑制CNE-2细胞诱导细胞凋亡的早期凋亡率分别为(22.26±1.37)%和(38.8±1.25)%,P值＜0.05。
5.0.5umol/mL的SMT与6μg/ml的顺铂共同干预CNE-2细胞,与正常组相比,两组NO的量分别为(9.05±0.02)umol/lVS(14.79±0.03)umol/l,有统计学差异。
结论:
1.SMT能够有效地呈浓度依赖性抑制CNE-2细胞的增殖。
2.SMT对顺铂的抗CNE-2细胞作用具有化疗增敏效应,其机制可能与NO的量有关,但具体增敏机制还有待进一步研究。
Objective:To investigate whether the selective iNOS inhibitor SMT can inhibit nasopharyngeal carcinoma cells CNE-2 proliferation,to investigate whether SMT can raise chemotherapy effect of cisplatin onCNE-2 cells and its mechanism.
Methods:
1 RT-PCR was used to detect the CNE-2 cell iNOS mRNA expression.
2 The effects of the different treatment(SMT,CDDP,CDDP+SMT) on CNE-2 cells proliferation were analyzed by MTT assay.
3 The morphology of cell apoptosis were analysed by HOECHST 33258 staining,and the cell apoptosis index(AI)were analysed by flow cytometry.
4 The amount of nitric oxide was determined by The Nitrate reductase asssy.
Results:
1.CNE-2 cells expressed iNOS,compared with high iNOS level of lung cancer cells A549.
2.SMT inhibited CNE-2 cells growth in a dose-dependent manner.
3.0.5 umol/mL SMT combined with 6μg/ml cisplatin inhibited CNE-2 cells proliferation and induced CNE-2 cells apoptosis more prominently than they treated CNE-2 cells respectively,CNE-2 cell apoptosis rates were(22.26±1.37)%VS(38.8±1.25)%.
4 Compared with the control group,the "SMT+cisplatin" obviously change the amount of nitric oxide.The amount of nitric oxide was (9.05±0.02)umol/l VS(14.79±0.03)umol/l.
Conclusion:
1.SMT inhibited CNE-2 cells growth in a dose dependent manner.
2.SMT can enhance the anti-cancer effects of cisplatin,the molecular mechanism may relate to the amount of nitric oxide,and the specific mechanisms have yet to be further studied.
观察诱导性一氧化氮合酶(iNOS)抑制剂SMT是否对鼻咽癌细胞株CNE-2有抑制细胞增殖能力和促进凋亡的能力,探讨SMT对顺铂的抗CNE-2细胞作用是否存在增敏效应及分子机制,为摸索治疗晚期鼻咽癌合理的药物组合提供实验依据。
方法:
1选用鼻咽癌细胞株CNE-2作为研究对象,以A549作为对照,RT-PCR测试CNE-2是否表达iNOS。
2用不同浓度的SMT、顺铂、二者合用作用于CNE-2细胞,干预CNE-2细胞后,MTT试验观察其对细胞活力的影响。
3 Hoechst33258染色观察细胞凋亡的形态学变化。
4流式细胞仪(FCM)检测细胞凋亡指数、凋亡的水平。
5硝酸还原酶法测NO的含量。
结果:
1.以iNOS高表达的肺癌细胞株A549为阳性对照,CNE-2细胞证实为iNOS阳性表达。
2.SMT以浓度依赖性方式有效地抑制CNE-2细胞增殖。
3.0.5umol/mL的SMT与6μg/ml的顺铂共同干预CNE-2细胞,较之单用SMT或顺铂抑制CNE-2细胞的凋亡形态学改变明显,凋亡小体以及核固缩现象增多。
4.0.5umol/mL的SMT与6μg/ml的顺铂共同干预CNE-2细胞,较之单用顺铂抑制CNE-2细胞诱导细胞凋亡的早期凋亡率分别为(22.26±1.37)%和(38.8±1.25)%,P值＜0.05。
5.0.5umol/mL的SMT与6μg/ml的顺铂共同干预CNE-2细胞,与正常组相比,两组NO的量分别为(9.05±0.02)umol/lVS(14.79±0.03)umol/l,有统计学差异。
结论:
1.SMT能够有效地呈浓度依赖性抑制CNE-2细胞的增殖。
2.SMT对顺铂的抗CNE-2细胞作用具有化疗增敏效应,其机制可能与NO的量有关,但具体增敏机制还有待进一步研究。
Objective:To investigate whether the selective iNOS inhibitor SMT can inhibit nasopharyngeal carcinoma cells CNE-2 proliferation,to investigate whether SMT can raise chemotherapy effect of cisplatin onCNE-2 cells and its mechanism.
Methods:
1 RT-PCR was used to detect the CNE-2 cell iNOS mRNA expression.
2 The effects of the different treatment(SMT,CDDP,CDDP+SMT) on CNE-2 cells proliferation were analyzed by MTT assay.
3 The morphology of cell apoptosis were analysed by HOECHST 33258 staining,and the cell apoptosis index(AI)were analysed by flow cytometry.
4 The amount of nitric oxide was determined by The Nitrate reductase asssy.
Results:
1.CNE-2 cells expressed iNOS,compared with high iNOS level of lung cancer cells A549.
2.SMT inhibited CNE-2 cells growth in a dose-dependent manner.
3.0.5 umol/mL SMT combined with 6μg/ml cisplatin inhibited CNE-2 cells proliferation and induced CNE-2 cells apoptosis more prominently than they treated CNE-2 cells respectively,CNE-2 cell apoptosis rates were(22.26±1.37)%VS(38.8±1.25)%.
4 Compared with the control group,the "SMT+cisplatin" obviously change the amount of nitric oxide.The amount of nitric oxide was (9.05±0.02)umol/l VS(14.79±0.03)umol/l.
Conclusion:
1.SMT inhibited CNE-2 cells growth in a dose dependent manner.
2.SMT can enhance the anti-cancer effects of cisplatin,the molecular mechanism may relate to the amount of nitric oxide,and the specific mechanisms have yet to be further studied.
引文
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