白芷香豆素类化合物对乳腺癌细胞的化疗增敏作用研究
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摘要
目的:探讨5种白芷香豆素类化合物欧前胡素、异欧前胡素、氧化前胡素、白当归脑、异补骨脂素对MCF-7、MDA-MB-231细胞的化疗增敏作用。方法:体外培养MCF-7、MDA-MB-231乳腺癌细胞,分别给予不同浓度的白芷香豆素类化合物欧前胡素、异欧前胡素、氧化前胡素、白当归脑以及异补骨脂素作用72 h,采用MTT法评价其对MCF-7和MDA-MB-231细胞增殖的影响。以最大无毒浓度的欧前胡素、异欧前胡素、氧化前胡素、白当归脑以及异补骨脂素联合不同浓度的阿霉素作用72 h,采用MTT法评价上述5种白芷香豆素类化合物与化疗药物阿霉素合用后对MCF-7和MDA-MB-231细胞增殖的影响。结果:5种白芷香豆素类化合物对MCF-7细胞的增殖有抑制作用,其中以欧前胡素和白当归脑作用最为明显,二者作用于MCF-7细胞72 h的IC_(50)值分别为68.24μg/mL和54.20μg/mL;欧前胡素、异欧前胡素、氧化前胡素和异补骨脂素对MDA-MB-231细胞增殖有抑制作用,以异欧前胡素和欧前胡素作用最明显,二者作用于MDA-MB-231细胞72 h的IC_(50)值分别为44.64μg/mL和71.11μg/mL,而白当归脑作用较弱。与不同浓度的阿霉素单独组比较,不同浓度的阿霉素与欧前胡素、氧化前胡素和白当归脑合用后对MCF-7和MDA-MB-231细胞的增殖抑制作用更为明显,IC_(50)明显降低,增敏倍数增加。结论:白芷香豆素类化合物欧前胡素、氧化前胡素和白当归脑对MCF-7和MDA-MB-231乳腺癌细胞具有化疗增敏作用。
AIM: To investigate the effects of coumarins from Angelica dahurica(imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, isopsoralen) on chemotherapeutic sensitivity of two different breast cancer cell lines, MCF-7 and MDA-MB-231. METHODS: MCF-7 and MDA-MB-231 cells were treated with different concentrations of imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, and isopsoralen for 72 h, respectively. The cytotoxity was evaluated by MTT assay.MCF-7 and MDA-MB-231 cells were treated with different doses of adriamycin in combination with the maximum nontoxic concentrations of imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, and isopsoralen for 72 h, respectively. The cytotoxity was evaluated by MTT assay. RESULTS:Five furanocoumarins, especially imperatorin, byakangelicolin caused an antiproliferative effect in MCF-7 cells. The IC_(50) values of imperatorin, byakangelicolin in MCF-7 cells at 72 h post-treatment were 68.24 μg/mL and 54.20 μg/mL, respectively. Imperatorin, isoimperatorin, oxypeucedanin and isopsoralen caused an antiproliferative effect in MDA-MB-231 cells. The IC_(50) values of isoimperatorin, imperatorin in MDA-MB-231 cells at 72 h post-treatment were 44.64 μg/mL and 71.11 μg/mL respectively. Byakangelicolin had weak or no effects on the proliferation. Compared with the adriamycin group, the inhibitory effect of adriamycin combined with imperatorin, isoimperatorin and byakangelicolin on the proliferation of MCF-7 and MDA-MB-231 cells was more obvious. The value of IC_(50) was decreased and the potentiation folds of adriamycin was increased.CONCLUSION: Imperatorin, oxypeucedanin and byakangelicol can inhibit proliferation of MCF-7 cells and MDA-MB-231 cells, and enhance the chemotherapeutic sensitivity.
AIM: To investigate the effects of coumarins from Angelica dahurica(imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, isopsoralen) on chemotherapeutic sensitivity of two different breast cancer cell lines, MCF-7 and MDA-MB-231. METHODS: MCF-7 and MDA-MB-231 cells were treated with different concentrations of imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, and isopsoralen for 72 h, respectively. The cytotoxity was evaluated by MTT assay.MCF-7 and MDA-MB-231 cells were treated with different doses of adriamycin in combination with the maximum nontoxic concentrations of imperatorin, isoimperatorin, oxypeucedanin, byakangelicol, and isopsoralen for 72 h, respectively. The cytotoxity was evaluated by MTT assay. RESULTS:Five furanocoumarins, especially imperatorin, byakangelicolin caused an antiproliferative effect in MCF-7 cells. The IC_(50) values of imperatorin, byakangelicolin in MCF-7 cells at 72 h post-treatment were 68.24 μg/mL and 54.20 μg/mL, respectively. Imperatorin, isoimperatorin, oxypeucedanin and isopsoralen caused an antiproliferative effect in MDA-MB-231 cells. The IC_(50) values of isoimperatorin, imperatorin in MDA-MB-231 cells at 72 h post-treatment were 44.64 μg/mL and 71.11 μg/mL respectively. Byakangelicolin had weak or no effects on the proliferation. Compared with the adriamycin group, the inhibitory effect of adriamycin combined with imperatorin, isoimperatorin and byakangelicolin on the proliferation of MCF-7 and MDA-MB-231 cells was more obvious. The value of IC_(50) was decreased and the potentiation folds of adriamycin was increased.CONCLUSION: Imperatorin, oxypeucedanin and byakangelicol can inhibit proliferation of MCF-7 cells and MDA-MB-231 cells, and enhance the chemotherapeutic sensitivity.
引文
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[19] 左陵君, 张耘新, 段建敏, 等. 苦参碱对人膀胱癌BIU-87/ADM细胞多药耐药的影响 [J]. 中国中医药信息杂志, 2016, 23(2): 73-75.
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[24] 杨秀伟, 徐波, 冉福香, 等. 40种香豆素类化合物对人表皮癌细胞系A432细胞株和人乳腺癌细胞系BCAP细胞株增殖抑制活性的筛选[J].中国现代中药, 2006, 8(12): 9-10.Effects of coumarins from Angelica dahurica
[2] 邓改改, 杨秀伟, 张友波, 等. 川白芷根脂溶性化学成分研究 [J]. 中国中药杂志, 2015, 40(11): 2148-2156.
[3] 邓改改, 杨秀伟, 张友波, 等. 禹白芷根脂溶性化学成分研究 [J]. 中国中药杂志, 2017, 42(11): 2102-2109.
[4] 秦旭华, 金沈锐, 唐怡, 等. 白芷总香豆素对偏头痛模型大鼠脑和血中一氧化氮和一氧化氮合酶的影响[J]. 成都中医药大学学报, 2012, 35(4): 5-7.
[5] 薛艳萍, 秦旭华, 胡黄婉莹, 等. 白芷总香豆素对偏头痛模型大鼠PGE2和TNFα的影响[J]. 中药与临床, 2016, 7(3): 42-44.
[6] 王世祥, 马晓毅, 贾璞, 等. 白芷总香豆素抗惊厥作用研究[J]. 中国医院药学杂志, 2016, 36(7): 561-564.
[7] 王萌, 陈建伟, 李祥. 明党参根皮中5种呋喃香豆素类成分的体外抗肿瘤活性[J]. 中国实验方剂学杂志, 2012, 18(6): 203-205.
[8] Donepudi MS, Kondapalli K, Amos SJ, et al. Breast cancer statistics and markers[J].J Cancer Res Ther,2014, 10(3): 506-511.
[9] Dubey AK, Gupta U, Jain S. Breast Cancer Statistics and Prediction Methodology: A Systematic Review and Analysis[J]. Asian Pacific Journal of Cancer Prevention,2015, 16(10): 4237-4245.
[10] Zeng H, Zheng R, Zhang S, et al. Female breast cancer statistics of 2010 in China: estimates based on data from 145 population-based cancer registries[J]. J Thorac Dis, 2014, 6(5): 466-470.
[11] 陈万青, 郑荣寿. 中国女性乳腺癌发病死亡和生存状况 [J]. 中国肿瘤临床, 2015, 42(13): 668-674.
[12] Liu SZ, Chen Q, Quan PL, et al. Cancer incidence and mortality in Henan province, 2012 [J]. Chin J Cancer Res,2016, 28(3): 275-285.
[13] 李云霞. 多西他赛治疗紫杉醇耐药乳腺癌的疗效 [J]. 现代仪器与医疗, 2016, 22(4): 31-32.
[14] 刘静, 陈开杰. 多西他赛为主的联合化疗方案治疗转移性乳腺癌 [J]. 现代仪器与医疗, 2016, 22(6): 117-118.
[15] 蔡加琴, 魏晓霞, 黄旭慧, 等. 氧化苦参碱通过调控上皮间质转化抑制三阴性乳腺癌细胞侵袭转移 [J]. 中国临床药理学与治疗学, 2018, 23(1): 13-17.
[16] 李晖, 陈俊, 徐彩虹, 等. 丹酚酸A抗肿瘤作用及对逆转A549/MTX肿瘤多药耐药的影响 [J]. 中国临床药理学与治疗学, 2017, 22(11): 1244-1247.
[17] 李絮, 代谊, 黄家凤, 等. 姜黄素通过调控组蛋白乙酰化修饰上调乳腺癌MCF-7和MCF-7/DOX细胞中MDR1表达 [J]. 中国临床药理学与治疗学, 2017, 22(5): 512-517.
[18] 周蓉蓉, 高鹏飞, 张文意, 等. 槐耳板蓝根双向发酵提取物抑制乳腺癌MCF-7细胞迁移/侵袭及相关因子的研究 [J]. 中国中医药信息杂志, 2016, 23(5): 64-68.
[19] 左陵君, 张耘新, 段建敏, 等. 苦参碱对人膀胱癌BIU-87/ADM细胞多药耐药的影响 [J]. 中国中医药信息杂志, 2016, 23(2): 73-75.
[20] 蒋洁敏, 康向东.姜黄素逆转紫杉醇耐药研究进展 [J].中国中医药信息杂志, 2016, 23(3): 129-133.
[21] Dong W, Liao ZG, Zhao GW, et al. Reversal Effect of Oxypeucedanin on P-glycoprotein-mediated Drug Transport [J]. Molecules, 2018, 23(8): pii: E1841.
[22] 董伟, 管雪静, 廖正根, 等. 白芷香豆素类化合物与P-糖蛋白体外亲和作用研究 [J]. 中草药, 2016, 47(16): 2893-2896.
[23] 陈虹. 欧前胡素体外诱导人乳腺癌细胞株MCF-7凋亡[J].浙江实用医学, 2015, 20(3): 177-179.
[24] 杨秀伟, 徐波, 冉福香, 等. 40种香豆素类化合物对人表皮癌细胞系A432细胞株和人乳腺癌细胞系BCAP细胞株增殖抑制活性的筛选[J].中国现代中药, 2006, 8(12): 9-10.Effects of coumarins from Angelica dahurica