苦参碱联合顺铂对人肝癌细胞株HepG2裸鼠移植瘤模型瘤体生长及caspase-3和Survivin表达的影响
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摘要
目的分析苦参碱联合顺铂对人肝癌细胞株Hep G2裸鼠移植瘤模型瘤体生长及半胱氨酸天冬氨酸蛋白酶-3(caspase-3)和存活素(Survivin)表达的影响。方法于BALB/c裸鼠腋部皮下注入人肝癌细胞株Hep G2以此构建移植瘤模型。在成瘤后,将28只裸鼠随机分为对照组(等量生理盐水)、顺铂组(顺铂2 mg/kg)、苦参碱组(苦参碱100 mg/kg)、联用组(苦参碱100 mg/kg+顺铂2 mg/kg)各7只,各组均通过腹腔注射给药。观察各组瘤体生长状况,对各组抑瘤率进行计算。通过免疫组化法对各组瘤组织中caspase-3、Survivin表达水平进行检测,计算和比较各组阳性细胞率。结果联用组裸鼠抑瘤率为80. 00%,较顺铂组(64. 00%)、苦参碱组(36. 00%)明显升高(P <0. 05)。联用组裸鼠caspase-3阳性细胞率为(77. 89±7. 35)%,较对照组(19. 89±4. 14)%、顺铂组(64. 86±9. 34)%、苦参碱组(36. 97±9. 35)%均显著上升(P <0. 05)。联用组裸鼠Survivin阳性细胞率为(20. 04±4. 37)%,较对照组(84. 85±14. 75)%、顺铂组(39. 05±7. 69)%、苦参碱组(64. 06±9. 14)%均显著降低(P <0. 05)。结论单用顺铂或苦参碱对人肝癌细胞株Hep G2裸鼠移植瘤均具有一定的抑瘤作用,但二者联用的抑瘤作用更为明显。其作用机制可能与苦参碱联合顺铂处理可对caspase-3、Survivin表达水平造成影响,进而促使肿瘤细胞凋亡存在密切关系。
Objective To analyze the effect of matrine combined with cisplatin on the growth of the tumor model of human hepatocellular carcinoma cell line HepG2 nude mice and the expression of cysteine aspartic proteinase-3( caspase-3) and Survivin( Survivin) in nude mice.Methods Human hepatoma cell line HepG2 was subcutaneously injected into the axilla of BALB/c nude mice to construct the transplanted tumor model. After tumor formation,28 nude mice were randomly divided into control group,cisplatin group,matrine group and combination group( matrine + cisplatin),with 7 cases in each group. All groups were injected by intraperitoneal injection. The growth status of each group was observed and the tumor inhibition rate was calculated. The expression levels of caspase-3 and Survivin in tumor tissues were detected by immunohistochemistry,and the positive cell rates in each group were calculated and compared. Results The inhibitory rate of nude mice in combination group was 80. 00%,which was significantly increased in comparison of cisplatin group( 64. 00%) and matrine group( 36. 00%)( P < 0. 05). The rate of caspase-3 positive cells in the nude mice was( 77. 89 ± 7. 35) %,which was significantly increased in comparison of the control group( 19. 89 ±4. 14) %,cisplatin group( 64. 86 ± 9. 34) %,and matrine group( 36. 97 ± 9. 35) %( P < 0. 05). The rate of Survivin positive cells in the nude mice was( 20. 04 ± 4. 37) %,which was significantly decreased in comparison of the control group( 84. 85 ± 14. 75) %,cisplatin group( 39. 05± 7. 69) %,and matrine group( 64. 06 ± 9. 14) %( P < 0. 05). Conclusion Cisplatin or matrine has a certain inhibitory effect on the tumor of human hepatoma cell line HepG2 nude mice,but the two combined tumor suppressor effect is more obvious. The effect of matrine and cisplatin on the expression of caspase-3 and Survivin may be affected by the combination of matrine and cisplatin,and the apoptosis of tumor cells is closely related.
Objective To analyze the effect of matrine combined with cisplatin on the growth of the tumor model of human hepatocellular carcinoma cell line HepG2 nude mice and the expression of cysteine aspartic proteinase-3( caspase-3) and Survivin( Survivin) in nude mice.Methods Human hepatoma cell line HepG2 was subcutaneously injected into the axilla of BALB/c nude mice to construct the transplanted tumor model. After tumor formation,28 nude mice were randomly divided into control group,cisplatin group,matrine group and combination group( matrine + cisplatin),with 7 cases in each group. All groups were injected by intraperitoneal injection. The growth status of each group was observed and the tumor inhibition rate was calculated. The expression levels of caspase-3 and Survivin in tumor tissues were detected by immunohistochemistry,and the positive cell rates in each group were calculated and compared. Results The inhibitory rate of nude mice in combination group was 80. 00%,which was significantly increased in comparison of cisplatin group( 64. 00%) and matrine group( 36. 00%)( P < 0. 05). The rate of caspase-3 positive cells in the nude mice was( 77. 89 ± 7. 35) %,which was significantly increased in comparison of the control group( 19. 89 ±4. 14) %,cisplatin group( 64. 86 ± 9. 34) %,and matrine group( 36. 97 ± 9. 35) %( P < 0. 05). The rate of Survivin positive cells in the nude mice was( 20. 04 ± 4. 37) %,which was significantly decreased in comparison of the control group( 84. 85 ± 14. 75) %,cisplatin group( 39. 05± 7. 69) %,and matrine group( 64. 06 ± 9. 14) %( P < 0. 05). Conclusion Cisplatin or matrine has a certain inhibitory effect on the tumor of human hepatoma cell line HepG2 nude mice,but the two combined tumor suppressor effect is more obvious. The effect of matrine and cisplatin on the expression of caspase-3 and Survivin may be affected by the combination of matrine and cisplatin,and the apoptosis of tumor cells is closely related.
引文
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[13]Li J,Hernanda PY,Bramer WM,et al.Anti-tumor effects of metformin in animal models of hepatocellular carcinoma:a systematic review and meta-analysis[J].PLo S One,201510(6):e0127967.
[14]李琦.苦参碱在抗肿瘤治疗中的研究进展[J].国际检验医学杂志,2017,38(4):500-502.
[15]Miyoshi H,Kato K,Iwama H,et al.Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo[J].Int J Oncol,2014,45(1):322-332.
[16]Shang MJ,Hong DF,Hu ZM,et al.Cisplatin induces apoptosis of hepatocellular carcinoma LM3 cells via down-regulation of XIAP[J].Eur Rev Med Pharmacol Sci,2018,22(2):382-387.
[2]陈建国,张永辉,朱健,等.启东肝癌的早诊早治及筛查效果评价[J].中华肿瘤杂志,2017,39(12):946-951.
[3]孙萌,邵亮,刘攀,等.姜黄素联合顺铂对HepG2肝癌细胞增殖、凋亡、迁移及侵袭的影响[J].中华实验外科杂志,2017,34(5):774-776.
[4]何永燕,遇珑,容雁,等.靶向上皮特异性抗原阳性肝癌干细胞单克隆抗体联合顺铂治疗肝癌的实验研究[J].中华肿瘤杂志,2016,38(5):333-339.
[5]Kamiyama T,Kakisaka T,Orimo T,et al.Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus[J].World J Hepatol,2017,9(36):1296-1304.
[6]张剑青,陈美霓,郭巍,等.17-AAG联合顺铂对人肝癌HepG2细胞增殖和凋亡的影响[J].山东医药,2015,55(38):7-9.
[7]胡静,周喜汉,胡高裕,等.苦参素联合顺铂对实验性肝癌miR-21、miR-122表达的影响[J].临床和实验医学杂志,2017,16(21):2084-2087.
[8]张晓莲,陈哲,邵安娜.苦参碱对人子宫内膜癌细胞增殖抑制的作用机制探究[J].临床和实验医学杂志,2018,17(8):822-825.
[9]王珂欣,高丽,周玉枝,等.苦参碱抗肝癌细胞增殖的1H-NMR代谢组学研究[J].中草药,2017,48(20):4275-4283.
[10]徐建,李敬东.肿瘤坏死因子相关凋亡诱导配体及其受体与肝癌[J].国际肿瘤学杂志,2013,40(8):605-607.
[11]Wang Y,Liu Y,Jiang J,et al.Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC-7721 cell line[J].Oncol Lett,2018,15(2):1777-1782.
[12]Miyata M,Morishita A,Sakamoto T,et al.MicroRNA profiles in cisplatin-induced apoptosis of hepatocellular carcinoma cells[J].Int J Oncol,2015,47(2):535-542.
[13]Li J,Hernanda PY,Bramer WM,et al.Anti-tumor effects of metformin in animal models of hepatocellular carcinoma:a systematic review and meta-analysis[J].PLo S One,201510(6):e0127967.
[14]李琦.苦参碱在抗肿瘤治疗中的研究进展[J].国际检验医学杂志,2017,38(4):500-502.
[15]Miyoshi H,Kato K,Iwama H,et al.Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo[J].Int J Oncol,2014,45(1):322-332.
[16]Shang MJ,Hong DF,Hu ZM,et al.Cisplatin induces apoptosis of hepatocellular carcinoma LM3 cells via down-regulation of XIAP[J].Eur Rev Med Pharmacol Sci,2018,22(2):382-387.