小檗碱联合人参皂苷Rg3对鼻咽癌裸鼠移植瘤细胞的干预作用

周芳亮, 蔺婷, 刘洁, 罗晶婧, 何迎春, 廖端芳

中国药学杂志 ›› 2021, Vol. 56 ›› Issue (18) : 1496-1502.

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中国药学杂志 ›› 2021, Vol. 56 ›› Issue (18) : 1496-1502. DOI: 10.11669/cpj.2021.18.009
论著

小檗碱联合人参皂苷Rg3对鼻咽癌裸鼠移植瘤细胞的干预作用

  • 周芳亮a,b,c, 蔺婷a, 刘洁a, 罗晶婧a,b, 何迎春a,b*, 廖端芳c
作者信息 +

The Effect of Berberine Combined with Ginsenoside Rg3 on Xenograft Model of Nasopharyngeal Carcinoma

  • ZHOU Fang-lianga,b,c, LIN Tinga, LIU Jiea, LUO Jing-jinga,b, HE Ying-chuna,b*, LIAO Duan-fangc
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文章历史 +

摘要

目的 探讨小檗碱与人参皂苷Rg3联合使用对鼻咽癌移植瘤的干预效应及可能机制。方法 建立鼻咽癌裸鼠移植瘤模型,观察小檗碱、人参皂苷Rg3单独或联合使用在体内的抑瘤效应;Tunel染色检测药物对体内肿瘤细胞凋亡的影响。Western blot、免疫组化检测小檗碱、人参皂苷Rg3单独或联合使用对体内细胞生存、增殖、凋亡相关蛋白及PI3K/AKT和MAPK/ERK信号通路关键蛋白表达的影响。结果 相较于对照组,小檗碱组、人参皂苷Rg3组、顺铂组以及联合用药组移植瘤重量明显下降,细胞凋亡率增加,且联合用药组效果优于两单药组。与单独用药组相比,联合用药组移植瘤组织的生存素survivin、增殖细胞核抗原PCNA、抗凋亡蛋白Bcl-2、p-AKT及p-ERK的表达均下调,促凋亡蛋白Bax表达上调(P<0.05)。结论 小檗碱、人参皂苷Rg3可协同抑制体内鼻咽癌CNE2移植瘤的生长,诱导移植瘤组织细胞的凋亡,其机制与PI3K/AKT和MAPK/ERK信号通路相关。

Abstract

OBJECTIVE To study the effect and possible mechanism of berberine combined with ginsenoside Rg3 on transplanted tumor of nasopharyngeal carcinoma. METHODS The antitumor effect of berberine or/and ginsenoside Rg3 were observed after establishing xenograft model of nasopharyngeal carcinoma. The effect of drugs on the apoptosis of tumor cells in vivo was examined by Tunel staining. Western blot and immunohistochemistry were used to examine the effects of berberine or/and ginsenoside Rg3 on the expressions of cell proliferation-, apoptosis-related proteins and key proteins of PI3K/AKT and MAPK/ERK in vivo. RESULTS Compared with the solvent control group, the weight of transplanted tumor in Berberine group, Ginsenoside Rg3 group, cisplatin group and combination group decreased significantly, while the apoptotic index was increased, and the effect of combined treatment group was better than that of two single drug groups. Compared with single drug group, the expressions of Survivin, PCNA,Bcl-2, p-AKT and p-ERK were down-regulated, while the expressions of Bax was up-regulated in the combined group (P<0.05). CONCLUSION Either single or combined use of berberine and ginsenoside Rg3 can synergistically inhibit the proliferation and induce cell apoptosis of NPC CNE2 cells in vivo. The mechanism is related to PI3K / Akt and MAPK / ERK signaling pathways.

关键词

小檗碱 / 人参皂苷Rg3 / 联合作用 / 鼻咽癌 / 裸鼠移植瘤

Key words

berberine / ginsenoside Rg3 / synergistic effect / nasopharyngeal carcinoma / xenograft model

引用本文

导出引用
周芳亮, 蔺婷, 刘洁, 罗晶婧, 何迎春, 廖端芳. 小檗碱联合人参皂苷Rg3对鼻咽癌裸鼠移植瘤细胞的干预作用[J]. 中国药学杂志, 2021, 56(18): 1496-1502 https://doi.org/10.11669/cpj.2021.18.009
ZHOU Fang-liang, LIN Ting, LIU Jie, LUO Jing-jing, HE Ying-chun, LIAO Duan-fang. The Effect of Berberine Combined with Ginsenoside Rg3 on Xenograft Model of Nasopharyngeal Carcinoma[J]. Chinese Pharmaceutical Journal, 2021, 56(18): 1496-1502 https://doi.org/10.11669/cpj.2021.18.009
中图分类号: R285.5   

参考文献

[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer J For Clin, 2018, 68(6):394-424.
[2] ZHOU Y J, MOU Y H, HU D S. An interpretation of CSCO/ASCO International Guideline of Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage Ⅱ-Ⅳa Nasopharyngeal Carcinoma in 2021[J]. Cancer Res Prev Treat(肿瘤防治研究), 2021:48(5):1-8.
[3] ZENG S R. Effect of Zengxiao Jiandu Decoction on prognosis and adverse reactions of nasopharyngeal carcinoma patients with radiotherapy and chemotherapy[J]. Chronic Pathematol J(慢性病学杂志), 2017, 18(7):795-797.
[4] HU M, TIAN D F, LIU Q L, et al. Antitumor Effect of Extract of Qi-Boosting Toxin-Resolving Formula on CNE2 Cell in Vitro and in Vivo[J]. Chin J Inf Tradit Chin Med(中国中医药信息杂志), 2012, 19(11):41-43.
[5] LIAN L X, KONG C Q, LUO J C, et al. Efficacy of riboflavin sodium phosphate combined with compound Kushen injection of radtioactive oral mucosal injury on nasopharyngeal carcinoma[J]. Mod Oncol(现代肿瘤医学), 2017, 25(24):3957-3961.
[6] LIU L, LUO N, GUO J, et al. Berberine inhibits growth and inflammatory invasive phenotypes of ectopic stromal cells: Imply the possible treatment of adenomyosis[J]. J Pharmacol Sci, 2018, 137(1):5-11.
[7] HESARI A, GHASEMI F, CICERO A F G, et al. Berberine: A potential adjunct for the treatment of gastrointestinal cancers [J]. J Cell Biochem, 2018, 119(12): 9655-9663.
[8] SUN M, YE Y, XIAO L, et al. Anticancer effects of ginsenoside Rg3 (Review)[J]. Inter J Mol Med, 2017, 39(3):507-518.
[9] ZHOU FL, HU J, DAI N, et al. Berberine and ginsenoside Rg3 act synergistically via the MAPK/ERK pathway in nasopharyngeal carcinoma cells[J]. J Funct Foods, 2020, 66(7):103802.
[10] LI CH, WU D F, DING H, et al. Berberine hydrochloride impact on physiological processes and modulation of twist levels in nasopharyngeal carcinoma CNE-1 cells[J]. Asian Pacific J Cancer Prevention, 2014, 15(4):1851-1857.
[11] JANTOVA S, CIPAK L, CERNAKOVA M, et al. Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cells[J]. J Pharm Pharmacol, 2003, 55(8):1143-1149.
[12] IIZUKA N, MIYAMOTO K, OKITA K, et al. Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines[J]. Cancer Lett, 2000, 148(1):19-25.
[13] CHEN H Z, LUO H N, QUAN B Y, et al. Effect of Rg3 on the expression of CD 80 /86 and cellular immune function in patients with nasopharyngeal carcinoma after radiotherapy[J]. Jilin J Tradit Chin Med(吉林中医药), 2017, 37(12): 1211-1214.
[14] SUN L R, HE S F, WANG R. Study of Ginsenoside Rg3 on Radiotherapy Sensitivity of Nasopharynx Cancer Stem Cells[J]. Pract J Cancer(实用癌症杂志), 2016, 31(7):1053-1055.
[15] WANG H B, LIN Y C, ZENG D, et al. Inhibitory effect of ginsenoside Rg3 on the tube-like structure formation in human nasopharyngeal carcinoma HNE-1 cell line in vitro[J]. Chin J Oncol, 2010, 32(10):739-742.
[16] KONG X, SHANG J L, ZHOU Y F, et al. 20(R)-ginsenoside Rg3 inhibits vasculogenic mimicry and cell migration of human nasopharyngeal carcinoma CNE-2 cell line in vitro[J]. Guangdong Med J (广东医学), 2015, 36(9):1314-1317.
[17] WANG Y, ZHONG J, BAI J, et al. The Application of Natural Products in Cancer Therapy by Targeting Apoptosis Pathways[J]. Curr Drug Metabol, 2018, 19(9):739-749.
[18] PFEFFER C M, SINGH A T K. Apoptosis: A Target for Anticancer Therapy[J]. Inter J Mol Sci, 2018, 19(2): 448.
[19] CAMPBELL K J, TAIT S W G. Targeting BCL-2 regulated apoptosis in cancer[J]. Open Biol, 2018, 8(5): 180002.
[20] CZABOTAR P E, LESSENE G, STRASSER A, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy[J]. Nat Rev Mol Cell Biol, 2014, 15(1):49-63.

基金

国家自然科学基金项目资助(81874408,81973914);湖南省中医药科研计划项目资助(2021174,2021014);湖南省教育厅优秀青年基金资助(19B439);湖南省自然科学基金项目资助(2019JJ40216,2020JJ5419);湖南省研究生优秀教学团队资助([2019]370-118);湖南省研究生创新课题资助(CX2018B482);中医药防治眼耳鼻咽喉疾病湖南省重点实验室开放基金课题资助(2018YZD04);湖南中医药大学基础医学一流学科开放基金课题资助(2018JCYX08)
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