Alopecurone B逆转人乳腺癌细胞MCF-7阿霉素耐药株活性研究
Reversal Effect and Mechanism of Alopecurone B on MCF-7 Adriamycin-Resistant Subline
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摘要: 目的 研究黄酮化合物Alopecurone B(APB)对人乳腺癌细胞阿霉素耐药株MCF-7/ADR多药耐药的逆转活性及逆转机制。方法 人乳腺癌细胞阿霉素耐药株MCF-7/ADR维持在含有250 ng/mL阿霉素的培养基中,使用MTT法、qPCR、Western blot和流式细胞术研究APB对耐药株P-糖蛋白(P-gp)功能和表达的影响。结果 APB能逆转MCF-7/ADR细胞多药耐药,抑制P-gp的功能,下调P-gp基因和蛋白的表达。结论 APB具有强效逆转人乳腺癌细胞MCF-7/ADR多药耐药的效果,其机制涉及对P-gp的调控。
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关键词:
- Alopecurone B /
- 阿霉素 /
- 乳腺癌 /
- 多药耐药 /
- P-糖蛋白
Abstract: OBJECTIVE To study the reversal effect and the mechanism of APB on adriamycin (ADR)-induced multidrug-resistant human breast cancer MCF-7/ADR cells. METHODS ADR-resistant MCF-7 cells were maintained in RPMI-1640 culture medium containing 10%FBS and 250 ng/mL ADR. MTT assay, qPCR, Western blot and flow cytometry were used to determine the inhibitory effect of APB on P-gp levels and function in MCF-7 or MCF-7/ADR cells. RESULTS APB reversed MCF-7/ADR multidrug resistance at the concentration of 10 μmol/L. Treated with 0, 5, 10, 20 μmol/L of ABP, P-gp gene and protein levels were suppressed significantly in a concentration-dependent manner. Furthermore, APB in 10 μmol/L markedly inhibited the function of P-gp. CONCLUSION APB potent reversed the multidrug resistance in MCF-7 ADR-resistant subline. The mechanism referred to P-gp inhibition.-
Key words:
- Alopecurone B /
- adriamycin /
- breast cancer /
- multidrug resistance /
- P-glycoprotein
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[1] HUANG S, HOLZEL M, KNIJNENBURG T, et al. MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling [J]. Cell, 2012, 151(5): 937-950. [2] ZHAO XQ, XIE JD, CHEN XG, et al. Neratinib reverses ATP-binding cassette B1-mediated chemotherapeutic drug resistance in vitro, in vivo<\i>, and ex vivo<\i>[J]. Mol Pharmacol, 2012, 82(1): 47-58. [3] 柴冰阳, 陈泽慧, 张闪闪,等. 4种细胞毒活性方法评价紫草素体外肿瘤细胞抑制作用效果[J]. 中草药, 2019, 50(1): 172-177. [4] 蒋卉男, 刘卓刚, 胡荣. Embelin逆转K562/D细胞对柔红霉素耐药与P-gp及MDR1 mRNA无关 [J]. 中国实验血液学杂志, 2017, 25(5): 1342-1349. [5] 卢善翃, 王芸芸, 李果,等. EphA2经P-糖蛋白调控鼻咽癌紫杉醇敏感性的实验研究 [J]. 中国耳鼻咽喉颅底外科杂志, 2018, 24(1): 33-38. [6] CHEN Q, BIAN Y, ZENG S. Involvement of AP-1 and NF- κB in the up-regulation of P-gp in vinblastine resistant Caco-2 cells [J]. Drug Metab Pharmacok, 2014, 29(2): 223-226. [7] 雷荣荣, 吴春珍. 天然产物逆转肿瘤多药耐药性研究进展 [J]. 世界临床药物, 2014, 35(8): 495-500. [8] ADES S, MAXFIELD LF, GOULD CJ, et al. Selection of non-P-glycoprotein mediated high-level etoposide resistant cell lines by adriamycin with P-gp inhibitors[J]. Int J Oncol, 2006, 28(3): 747-753. [9] GILL J, AHLUWALIA MK, GELLER D, et al. New targets and approaches in osteosarcoma[J]. Pharmacol Ther, 2013, 137(1): 89-99. [10] ZHU XZ, WONG ILK, CHAN KF, et al. Triazole bridged flavonoid dimers as potent, nontoxic, and highly selective breast cancer resistance protein (BCRP/ABCG2) inhibitors[J]. J Med Chem, 2019, 62(18): 8578-8608. [11] KO JH, SETHI G, UM JY, et al. The role of resveratrol in cancer therapy [J]. Int J Mol Sci, 2017, 18(12): 2589. [12] XIA YZ, NI K, GUO C, et al. Alopecurone B reverses doxorubicin-resistant human osteosarcoma cell line by inhibiting P-glycoprotein and NF-kappa B signaling[J]. Phytomedicine, 2015, 22(3): 344-351. [13] IINUMA M, OHYAMA M, TANAKA T. 6 flavonostilbenes and a flavanone in roots of sophora-alopecuroides[J]. Phytochemistry, 1995, 38(2): 519-525. [14] XIA YZ, YANG L, WANG ZD, et al. Schisandrin A enhances the cytotoxicity of doxorubicin by the inhibition of nuclear factor-kappa B signaling in a doxorubicin-resistant human osteosarcoma cell line [J]. Rsc Adv, 2015, 5(18): 13972-13984. [15] ZHOU XW, XIA YZ, ZHANG YL, et al. Tomentodione M sensitizes multidrug resistant cancer cells by decreasing P-glycoprotein via inhibition of p38 MAPK signaling[J]. Oncotarget, 2017, 8(60): 101965-101983. [16] 崔美英, 贺红柳, 李盼,等. 柚皮苷对人肺癌顺铂耐药株A549/DDP细胞的逆转作用 [J]. 中国病理生理杂志, 2019, 35(3): 466-472.
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