基于ATP7A探讨粉防己碱对乳腺癌细胞顺铂耐药的逆转作用及机制
|
摘要
目的基于ATP7A探讨粉防己碱对乳腺癌细胞顺铂耐药的逆转作用及机制。方法建立两种人乳腺癌顺铂耐药细胞株及ATP7A高表达细胞。检测粉防己碱对顺铂耐药细胞的逆转作用,高效液相色谱测定胞内顺铂含量,检测ATP7A蛋白表达。结果耐药乳腺癌细胞的顺铂敏感性显著降低(P <0.05),ATP7A表达升高(P <0.05),胞内顺铂含量明显降低(P <0.05);ATP7A高表达细胞较正常乳腺癌细胞顺铂敏感性下降(P <0.05),胞内顺铂含量降低(P <0.05)。而粉防己碱对细胞耐药性具有明显的逆转作用,较耐药细胞及转染细胞可升高胞中顺铂含量(P <0.05),降低ATP7A表达(P <0.05)。结论粉防己碱对人乳腺癌顺铂耐药细胞及ATP高表达细胞的顺铂耐药性有逆转作用,其机制可能与抑制ATP7A表达相关。
Objective To explore the reversal effect and mechanism of tetrandrine for Cisplatin-resistant breast cancer cells based on ATP7 A. Methods Two kinds of human Cisplatin-resistant breast cancer cells lines and cells with high expression of ATP7 A were established to detect the reversal effects of tetrandrine on Cisplatin-resistant breast cancer cells. The intracellular content of Cisplatin was determined by high performance liquid chromatography and the expression of ATP7 A protein was detected. Results The sensitivity of Cisplatin in resistant breast cancer cells was significantly decreased(P < 0.05), the expression of ATP7 A protein was increased(P < 0.05), and the intracellular content of Cisplatin was decreased significantly(P < 0.05); compared with normal breast cancer cells, the sensitivity of Cisplatin in cells with high expression of ATP7 A significantly decreased(P < 0.05), and the intracellular content of Cisplatin was decreased significantly(P < 0.05). Tetrandrine had significant reversal effects for the drug resistance of cells, which could increase the intracellular content of Cisplatin(P < 0.05), and decrease the expression of ATP7 A compared with drug-resistant cells and transfected cells(P < 0.05). Conclusion Tetrandrine has reversal effects for human Cisplatinresistant breast cancer cells lines and cells with high expression of ATP7 A, its mechanism may be related to the inhibition of ATP7 A expression.
Objective To explore the reversal effect and mechanism of tetrandrine for Cisplatin-resistant breast cancer cells based on ATP7 A. Methods Two kinds of human Cisplatin-resistant breast cancer cells lines and cells with high expression of ATP7 A were established to detect the reversal effects of tetrandrine on Cisplatin-resistant breast cancer cells. The intracellular content of Cisplatin was determined by high performance liquid chromatography and the expression of ATP7 A protein was detected. Results The sensitivity of Cisplatin in resistant breast cancer cells was significantly decreased(P < 0.05), the expression of ATP7 A protein was increased(P < 0.05), and the intracellular content of Cisplatin was decreased significantly(P < 0.05); compared with normal breast cancer cells, the sensitivity of Cisplatin in cells with high expression of ATP7 A significantly decreased(P < 0.05), and the intracellular content of Cisplatin was decreased significantly(P < 0.05). Tetrandrine had significant reversal effects for the drug resistance of cells, which could increase the intracellular content of Cisplatin(P < 0.05), and decrease the expression of ATP7 A compared with drug-resistant cells and transfected cells(P < 0.05). Conclusion Tetrandrine has reversal effects for human Cisplatinresistant breast cancer cells lines and cells with high expression of ATP7 A, its mechanism may be related to the inhibition of ATP7 A expression.
引文
[1] Mandala M,Tondini C. Adjuvant therapy in breast cancer and venous thromboembolism[J]. Thromb Res,2012,130(1):66-70.
[2] Li ZF,Wang SM,Shi JF,et al. Combined screening of cervical cancer,breast cancer and reproductive tract infections in rural China[J]. Asian Pac J Cancer Prev,2012,13(7):3529-3533.
[3] Galluzzi L,Vitale I,Michels J,et al. Systems biology of cisplatin resistance:past,present and future[J]. Cell Death Dis,2014,5:e1257.
[4] Arslan C,Ozdemir E,Altundag K,et al. Secondary hematological malignancies after treatment of non-metastatic breast cancer[J]. J Buon,2011,16(4):744-750.
[5]刘嘉琪,张雅男,赵婉,等.粉防己化学成分及药理学研究进展[J].中医药学报,2017,45(3):100-103.
[6]韩彬,王国俊,罗恒丽.粉防己碱药理作用研究进展[J].临床合理用药,2014,7(3):198-199.
[7]闫冠韫,王立波,程伟.中药抗肿瘤生物碱类药物的研究进展[J].中医药学报,2013,41(2):101-103.
[8]陈晓松,包明红,梅晓冬.粉防己碱对人口腔上皮癌多药耐药KB-MRP1细胞株多药耐药性的逆转作用[J].癌症,2007,26(8):846-850.
[9]李海燕,陈阳,何琪杨.苦参碱与粉防己碱逆转人MCF-7细胞耐药性的作用与机制[J].中国实验方剂学杂志,2013,19(18):275-278.
[10]盛佳钰,时百玲,陈红风.三阴性乳腺癌MDA-MB-231顺铂耐药细胞株的建立及鉴定[J].肿瘤防治研究,2016,43(3):175-180.
[11]周琼,郁韵秋.高效液相色谱法测定乳剂中顺铂含量[J].中国医院药学杂志,1999,19(2):78-80.
[12] Weiss RB,Christian MC. New cisplatin analogues in development. A review[J]. Drugs,1993,46(3):360-377
[13]朱星枚,吴琳,张媛,等.细胞自噬与人卵巢癌细胞对顺铂耐药的关系[J].中国医药导报,2016,13(25):12-16.
[14] Jakupec MA,Galanski M,Keppler BK. Tumour-inhibiting platinum complexes-state of the art and future perspectives[J]. Rev Physiol Biochem Pharmacol,2003,146(6):1-53.
[15] Natile G,Coluccia M. Current status of trans-platinum compounds in cancer therapy[J]. Coordination Chemistry Reviews,2001,216(6):383-410.
[16] Zhang Y,LiM,Yao Q,et al. Roles and mechanisms of coppertran sporting ATPases in cancer pathogenesis[J].Med Sci Monit,2009,15(1):RA1-RA5.
[17] Leonhardt K,Gebhardt R,M觟ssner J,et al. Functional Interactions of Cu-ATPase ATP7B with Cisplatin and the Role of ATP7B in the Resistance of Cells to the Drug[J].J Biol Chem,2009,284(12):7793-7802.
[18] Kuo MT,Chen HH,Song IS,et al. The roles of copper transporters in cisplatin resistance[J]. Cancer Metastasis Rev,2007,26(1):71-83.
[19]邢志博,王凤梅,王翠平,等.粉防己有效成分的药理活性研究进展[J].中国实验方剂学杂志,2014,20(9):241-246.
[20] He QY,Meng FH,Zhang HQ. Reduction of doxorubicin resistance by tet randrine and dauricine in harringtonine-resistant human leukemia(HL60)cells[J]. Acta Pharmacologica Sinica,1996,7(2):179-181.
[2] Li ZF,Wang SM,Shi JF,et al. Combined screening of cervical cancer,breast cancer and reproductive tract infections in rural China[J]. Asian Pac J Cancer Prev,2012,13(7):3529-3533.
[3] Galluzzi L,Vitale I,Michels J,et al. Systems biology of cisplatin resistance:past,present and future[J]. Cell Death Dis,2014,5:e1257.
[4] Arslan C,Ozdemir E,Altundag K,et al. Secondary hematological malignancies after treatment of non-metastatic breast cancer[J]. J Buon,2011,16(4):744-750.
[5]刘嘉琪,张雅男,赵婉,等.粉防己化学成分及药理学研究进展[J].中医药学报,2017,45(3):100-103.
[6]韩彬,王国俊,罗恒丽.粉防己碱药理作用研究进展[J].临床合理用药,2014,7(3):198-199.
[7]闫冠韫,王立波,程伟.中药抗肿瘤生物碱类药物的研究进展[J].中医药学报,2013,41(2):101-103.
[8]陈晓松,包明红,梅晓冬.粉防己碱对人口腔上皮癌多药耐药KB-MRP1细胞株多药耐药性的逆转作用[J].癌症,2007,26(8):846-850.
[9]李海燕,陈阳,何琪杨.苦参碱与粉防己碱逆转人MCF-7细胞耐药性的作用与机制[J].中国实验方剂学杂志,2013,19(18):275-278.
[10]盛佳钰,时百玲,陈红风.三阴性乳腺癌MDA-MB-231顺铂耐药细胞株的建立及鉴定[J].肿瘤防治研究,2016,43(3):175-180.
[11]周琼,郁韵秋.高效液相色谱法测定乳剂中顺铂含量[J].中国医院药学杂志,1999,19(2):78-80.
[12] Weiss RB,Christian MC. New cisplatin analogues in development. A review[J]. Drugs,1993,46(3):360-377
[13]朱星枚,吴琳,张媛,等.细胞自噬与人卵巢癌细胞对顺铂耐药的关系[J].中国医药导报,2016,13(25):12-16.
[14] Jakupec MA,Galanski M,Keppler BK. Tumour-inhibiting platinum complexes-state of the art and future perspectives[J]. Rev Physiol Biochem Pharmacol,2003,146(6):1-53.
[15] Natile G,Coluccia M. Current status of trans-platinum compounds in cancer therapy[J]. Coordination Chemistry Reviews,2001,216(6):383-410.
[16] Zhang Y,LiM,Yao Q,et al. Roles and mechanisms of coppertran sporting ATPases in cancer pathogenesis[J].Med Sci Monit,2009,15(1):RA1-RA5.
[17] Leonhardt K,Gebhardt R,M觟ssner J,et al. Functional Interactions of Cu-ATPase ATP7B with Cisplatin and the Role of ATP7B in the Resistance of Cells to the Drug[J].J Biol Chem,2009,284(12):7793-7802.
[18] Kuo MT,Chen HH,Song IS,et al. The roles of copper transporters in cisplatin resistance[J]. Cancer Metastasis Rev,2007,26(1):71-83.
[19]邢志博,王凤梅,王翠平,等.粉防己有效成分的药理活性研究进展[J].中国实验方剂学杂志,2014,20(9):241-246.
[20] He QY,Meng FH,Zhang HQ. Reduction of doxorubicin resistance by tet randrine and dauricine in harringtonine-resistant human leukemia(HL60)cells[J]. Acta Pharmacologica Sinica,1996,7(2):179-181.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |