湖南中医药大学, a. 中医药防治眼耳鼻咽喉疾病湖南省重点实验室, b. 医学院, c. 湘产大宗药材品质评价湖南省重点实验室, 长沙 410208
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
a. Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, b. College of Medicine, c. Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province State, Hunan University of Chinese Medicine, Changsha 410208, China
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.
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.
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. Chinese Pharmaceutical Journal, 2021, 56(18): 1496-1502.
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.