Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (3): 275-280.doi: 10.3736/jcim20060311

• Original Experimental Research • Previous Articles     Next Articles

Effects of Jinlongshe Granules on apoptosis of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice

Zhi-hong Yu, Pin-kang Wei, Ling Xu, Zhi-feng Qin, Jun Shi, Yan Xiao, Hui-ming Lin   

  1. Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  • Online:2006-05-31 Published:2006-05-15


To assess the effects of Jinlongshe Granules (JLSG) on tumor growth of gastric carcinoma.


Fifty nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were divided into five groups: untreated group, 5-fluorouracil (5-FU)-treated group and high-, medium-, and low-dose JLSG-treated groups. Corresponding antitumor drugs were administered in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM) and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining assay. The ultrastructure of MKN-45 gastric cancer cells was observed by transmission electron microscope.


In the mice treated with high-, medium-, and low-dose JLSG, the growth inhibition rates of gastric cancer were 68.13%, 55.94% and 50.31% respectively, and this antitumor effect was dose-dependent. In the mice treated with intraperitoneal injection of 5-FU, the growth inhibition rate of gastric cancer was 53.43% and not much different from those treated with JLSG. The apoptotic rates in the high-, medium-, and low-dose JLSG-treated groups were 22.81%, 28.27% and 38.54% respectively, in a dose-dependent manner, with the cell cycle arrested at G0/G1 phase. An Annexin V-FITC/PI staining assay revealed that the percentages of early apoptotic cells in the three dose JLSG-treated groups were all significantly higher than that in the 5-FU-treated group, whereas the late apoptotic and necrotic cells were much more in the 5-FU-treated group than those in the three dose JLSG-treated groups.


Jinlongshe Granules exert an inhibiting effect on MKN-45 human gastric cancer cells orthotopically transplanted in nude mice by promoting the cell apoptosis.

Key words: Jinlongshe Granules, Stomach neoplasms, Orthotopic transplantation, Cell cycle, Apoptosis, Traditional Chinese medicine and pharmacy, Nude mouse, Huma

CLC Number: 

  • R735.2

Table 1

Antitumor effects on orthotopically transplanted gastric cancer in nude mice in different groups(ヌ±S )"

Group n Tumor weight (?x±s, g) Growth inhibition rate (%)
Untreated 10 3.20±0.96
High-dose JLSG-treated 10 1.02±0.57** 68.13
Medium-dose JLSG-treated 10 1.41±1.39** 55.94
Low-dose JLSG-treated 10 1.59±1.12** 50.31
5-FU-treated 8 1.49±1.37** 53.43

Figure 1

Ultrastructures of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groupsA: Untreated group (×4 000); B: Medium-dose JLSG-treated group (×6 000); C: 5-FU-treated group (×3 000)."

Table 2

Cell cycle distribution and apoptotic rate of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groups (ヌ±S )"

Group n G0/G1 G2/M S Apoptotic rate
Untreated 10 42.40±11.28 21.28±11.43 36.92±12.21 19.88±14.83
High-dose JLSG-treated 10 50.58±8.78 26.45±12.53 14.56±9.35* 38.54±12.65
Medium-dose JLSG-treated 10 47.55±7.02 26.51±15.05 19.36±12.69* 28.27±11.25
Low-dose JLSG-treated 10 46.37±12.09 25.47±14.79 24.04±13.27* 22.81±10.65
5-FU-treated 8 41.78±4.30 23.59±11.97 19.97±13.31* 24.97±9.93

Figure 2

Classification percentage of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groups by Annexin V-FITC/PI staining assay and flow cytometryA: High-dose JLSG-treated group; B: Medium-dose JLSG-treated group; C: Low-dose JLSG-treated group;D: Untreated group; E: 5-FU-treated group."

Table 3

Classification percentage of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groups by Annexin V-FITC/PI staining assay and flow cytometry (ヌ±S, %)"

Group n Damaged cells Late apoptotic cells and Living cells Early apoptotic
(in LUQ) necrotic cells (in RUQ) (in LLQ) cells (in RLQ)
Untreated 10 22.19±7.73 12.58±6.94 63.99±6.36 1.56±1.37
High-dose JLSG-treated 10 26.26±2.29 11.76±2.72 50.12±4.53* 12.21±4.45*
Medium-dose JLSG-treated 10 27.25±5.83* 12.02±8.96 54.23±10.14* 5.90±4.41*
Low-dose JLSG-treated 10 27.63±6.54* 11.51±6.40 55.70±7.60* 4.47±3.20
5-FU-treated 8 27.18±6.99 13.22±7.14 52.77±12.68* 6.76±3.98*
[1] Hohenberger P, Gretschel S . Gastric cancer[J]. Lancet, 2003,362(9380):305-315
[2] Howson CP, Hiyama T , Wynder EL.The decline of gastric cancer: epidemiology of an unplanned triumph[J]. Epidemiol Rev, 1986, 8. 1-27
doi: 10.1146/annurev.publhealth.7.1.535 pmid: 3533579
[3] Kelley JR, Duggan JM . Gastric cancer epidemiology and risk factors[J]. J Clin Epidemiol, 2003,56(1):1-9
doi: 10.1016/S0895-4356(02)00534-6 pmid: 12589864
[4] Alberts SR, Cervantes A, van de Velde CJ , Gastric cancer: epidemiology,pathology and treatment[J].Ann Oncol 2003, 14(Suppl 2):ii31- ii36
[5] 许玲, 陈亚琳, 苏晓妹 , 等. 裸鼠人胃腺癌SGC-7901原位移植模型的构建及其生物学特性[J]. 肿瘤防治杂志, 2003,10(5):476-478
[6] 王北婴, 李仪奎 . 中药新药研制开发技术与方法(第1版)[M]. 上海: 上海科学技术出版社, 2001,( 第1版):737
[7] van Engeland M, Nieland LJ, Ramaekers FC , et al. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure[J]. Cytometry, 1998,31(1):1-9
[8] 雷晓, 余佩武 . 双标记流式细胞术定量分析5-FU诱导胃癌细胞早期凋亡[J]. 第三军医大学学报, 2002,24(7):855-857
[9] Kamesaki H . Mechanisms involved in chemotherapy-induced apoptosis and their implications in cancer chemotherapy[J]. Int J Hematol, 1998,68(1):29-43
[10] Reed JC . Apoptosis-targeted therapies for cancer[J]. Cancer Cell, 2003,3(1):17-22
doi: 10.1016/S1535-6108(02)00241-6 pmid: 12559172
[11] Alison MR, Sarraf CE . Apoptosis: regulation and relevance to toxicology[J]. Hum Exp Toxicol, 1995,14(3):234-247
doi: 10.1177/096032719501400302 pmid: 7779453
[12] 赵爱光, 杨金坤, 赵海磊 , 等. 四君子汤诱导裸小鼠移植性人胃癌细胞凋亡的初步研究[J]. 癌症, 2001,20(2):164-167
[13] Liu W, Guo QL, You QD , et al. Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823[J]. World J Gastroenterol, 2005,11(24):3655-3659
[14] Yin X, Zhou J, Jie C , et al. Anticancer activity and mechanism of Scutellaria barbata extract on human lung cancer cell line A549[J]. Life Sci, 2004,75(18):2233-2244
[15] Shao QS, Ye ZY, Ling ZQ , et al. Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma cells mediated by arsenic trioxide[J]. World J Gastroenterol, 2005,11(22):3451-3456
[16] 周俊 . 中药复方——天然组合化学库与多靶作用机理[J]. 中国中西医结合杂志, 1998,18(2):67
[17] 赵健雄, 程卫东, 徐瑞峰 , 等. 扶正抑瘤颗粒药物血清诱导小鼠肝癌细胞凋亡及其机制的研究[J]. 中西医结合学报, 2005,3(4):278-281
doi: 10.3321/j.issn:1003-5370.2003.12.008
[18] 魏品康, 许玲, 秦志丰 , 等. 胃癌从痰论治的机制与临床研究[J]. 中国中医基础医学杂志, 2002,13(3):18-20
[19] 李相勇, 魏品康 . 金龙蛇口服液治疗晚期胃癌的疗效观察[J]. 湖北中医杂志, 2001,23(11):3-5
doi: 10.3969/j.issn.1000-0704.2001.11.001
[20] 秦志丰, 魏品康, 李相勇 . 金龙蛇口服液合参麦注射液对中晚期胃癌患者肿瘤标志物和免疫功能的影响[J]. 中医杂志, 2001,42(10):605-606
[21] 许玲, 陈亚琳, 刘咏英 , 等. 金龙蛇口服液合华蟾素注射液、黄芪注射液治疗Ⅳ期胃癌的临床观察[J]. 成都中医药大学学报, 2005,28(1):7-9
doi: 10.3969/j.issn.1004-0668.2005.01.003
[22] 许玲, 魏品康, 陈亚琳 , 等. 中药消痰散结方抑制裸鼠原位移植人胃癌SGC-7901的生长转移[J]. 世界华人消化杂志, 2004,12(5):1015-1020
doi: 10.3969/j.issn.1009-3079.2004.05.002
[23] 肖艳, 魏品康, 许玲 , 等. 消痰散结方对裸鼠MKN-45人胃癌组织中MMP2表达的影响[J]. 成都中医药大学学报, 2002,25(4):32-33
doi: 10.3969/j.issn.1004-0668.2002.04.014
[24] 许玲, 苏晓妹, 陈亚琳 , 等. 中药消痰散结方对人胃癌裸鼠原位移植瘤VEGF, KDR mRNA表达的影响[J]. 世界华人消化杂志, 2004,1(4):988-990
doi: 10.3969/j.issn.1009-3079.2004.04.060
[1] Cai-lian Fana, Wan-jun Caib, Meng-nan Ye, Miao Chen, Yi Dai. Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro. Journal of Integrative Medicine, 2022, 20(4): 365-375.
[2] Hong-xiao Li, Ling Shi, Shang-jie Liang Chen-chen Fang, Qian-qian Xu, Ge Lu, Qian Wang, Jie Cheng, Jie Shen, Mei-hong Shen. Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of Integrative Medicine, 2022, 20(2): 163-172.
[3] Mohamed S. Othman, Sofian T. Obeidat, Amal H. Al-Bagawi, Mohamed A. Fareid, Alaa Fehaid, Ahmed E. Abdel Moneim. Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent#br#
. Journal of Integrative Medicine, 2022, 20(1): 65-72.
[4] Hyongjun Jeon, Hee-Young Kim, Chang-Hwan Bae, Yukyung Lee, Sungtae Koo, Seungtae Kim. Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells. Journal of Integrative Medicine, 2021, 19(6): 537-544.
[5] Porwornwisit Tritripmongkol, Tullayakorn Plengsuriyakarn, Mayuri Tarasuk, Kesara Na-Bangchang. In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma. Journal of Integrative Medicine, 2020, 18(4): 326-333.
[6] Varuni Colamba Pathiranage, Ira Thabrew, Sameera R. Samarakoon, Kamani H. Tennekoon, Umapriyatharshini Rajagopalan, Meran K. Ediriweera. Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells. Journal of Integrative Medicine, 2020, 18(3): 242-252.
[7] Maged Mohamed Maher Abou-Hashem, Dina Mohamed Abo-elmatty, Noha Mostafa Mesbah, Ahmed Mohamed Abd EL-Mawgoud. Induction of sub-G0 arrest and apoptosis by seed extract of Moringa peregrina (Forssk.) Fiori in cervical and prostate cancer cell lines. Journal of Integrative Medicine, 2019, 17(6): 410-422.
[8] Lena Grönblom Lundström, Ulrika Aasa, Yan Zhang, Tobias Sundberg. Health care in light of different theories of health—A proposed framework for integrating a social humanistic perspective into health care. Journal of Integrative Medicine, 2019, 17(5): 321-327.
[9] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Apirada Sucontphunt, Mattaka Khongkow, Thongchai Koobkokkruad, Nontima Vardhanabhuti. Flavonoids kaempferide and 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells. Journal of Integrative Medicine, 2019, 17(4): 288-295.
[10] Fang-yuan Wang, Jian Jia, Huan-huan Song, Cheng-ming Jia, Chang-bo Chen, Jing Ma. Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress. Journal of Integrative Medicine, 2019, 17(3): 205-212.
[11] Shriniwas S. Basaiyye, Sanjay Kashyap, Kannan Krishnamurthi, Saravanadevi Sivanesan. Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.). Journal of Integrative Medicine, 2019, 17(3): 221-228.
[12] Carlos R. Oliveira, Daniel G. Spindola, Daniel M. Garcia, Adolfo Erustes, Alexandre Bechara, Caroline Palmeira-dos-Santos, Soraya S. Smaili, Gustavo J.S. Pereira, André Hinsberger, Ezequiel P. Viriato, Maria Cristina Marcucci, Alexandra C.H.F. Sawaya, Samantha L. Tomaz, Elaine G. Rodrigues, Claudia Bincoletto. Medicinal properties of Angelica archangelica root extract: Cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development. Journal of Integrative Medicine, 2019, 17(2): 132-140.
[13] Bruno José Martins Da Silva, Sandro Wilson Gomes Pereira, Ana Paula Drummond Rodrigues, José Luiz Martins Do Nascimento, Edilene Oliveira Silva. In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum. Journal of Integrative Medicine, 2018, 16(6): 404-410.
[14] Rohitash Jamwal. Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers. Journal of Integrative Medicine, 2018, 16(6): 367-374.
[15] Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan . Casticin from Vitex species: A short review on its anticancer and anti-inflammatory properties. Journal of Integrative Medicine, 2018, 16(3): 147-152.
Full text



[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228