[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (4): 378-383.doi: 10.3736/jcim20060412

• Original Experimental Research • Previous Articles     Next Articles

Effects of interventional therapy with norcantharidin microsphere on hepatoma in rats and its mechanism

Qi Li1, Zhong-ze Fan1, Xian-qian Li1, Xiao-hua Liu2, Jue Sun1, Wei Gu3, Paul Heng2, Hong Gao1   

  1. 1. Department of Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
    2. Department of Pharmacy, National University of Singapore, Singapore
    3. Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
  • Online:2006-07-31 Published:2006-07-15

RichHTML

1

PDF (PC)

483

Like

Objective

o investigate the effects of interventional therapy with norcantharidin-alginic acid/poly acid anhydride microspheres (N-MS) infusion via hepatic artery on hepatoma in rats.

Methods

-MS was prepared by emulsion-chemical crosslink technique. Eighty-nine hepatoma-bearing rats were randomly divided into five groups, which were normal saline group, norcantharidin (NCTD) group, blank microsphere (B-MS) group, NCTD-lipiodol group and N-MS group. Normal saline, NCTD, B-MS, NCTD-lipiodol and N-MS were injected via hepatic artery accordingly. After the interventional therapy, eight rats from each group were observed for survival time, and the rest rats were killed on the 8th day after intervention to measure the tumor volume and necrostic degree. The apoptotic index of liver tumor cells was detected by TUNEL staining, and the expression of ki-67 was assayed by immuno-histochemical streptavidin-biotin peroxidase method.

Results

The survival time of the rats in the N-MS group was prolonged as compared with those in the other four groups, and the tumor volume of the rats in the N-MS group was smaller than those in the other four groups. The tumor growth rate and the expression level of ki-67 in the N-MS group were both significantly lower than those in the other four groups. The tumor necrotic degree and the apoptotic index in the N-MS group were significantly higher than those in the other four groups.

Conclusion

Interventional therapy with N-MS could yield preferable therapeutic effects on hepatomas in rats. This anti-tumor efficacy may be associated with microvessel embolization in liver tumor and the sustained releasing of NCTD. Its inhibiting effect on tumor cell proliferation maybe result from decreasing the expression of Ki-67 and inducing the tumou cell apoptosis.

Key words: Liver neoplasms, Interventional therapy, Microsphere, Norcantharidin, Alginic acid, poly acid anhydride, Animals, Laboratory

CLC Number: 

  • R735.7

Table 1

Pre- and post-TACE liver tumor volume and tumor growth rate of rats in different groups（ヌ±S ）"

Group n Liver tumor volume (mm3) Tumor growth rate
Pre-treatment Post-treatment
Normal saline 8 79.01±29.57 1 586.63±831.22△△▲▲ 21.96±13.78△△
NCTD 9 70.97±27.59 796.94±603.83**△△▲▲ 11.20±7.22**△△
B-MS 7 80.21±29.42 684.14±405.68**△△▲▲ 8.01±8.68**△△
N-MS 10 79.20±30.75 62.55±32.09** 0.79±0.90**
NCTD-lipiodol 7 73.91±26.01 122.29±69.60**△△ 1.84±1.22△△

Table 2

Necrotic degree of liver tumor in rats after TACE in different groups"

Group n Necrotic degree of liver tumor
Mild degree Moderate degree Severe degree
Normal saline** 8 7 1 0
NCTD** 9 4 5 0
B-MS** 7 2 4 1
N-MS 10 0 2 8
NCTD-lipiodol** 7 2 3 2

Table 3

Survival time and life prolonged rate of rats with liver tumor after TACE in different groups（ヌ±S ）"

Group n Survival time (d) Life prolonged rate (%)
Normal saline 8 14.50±2.39△△ —
NCTD 8 16.25±1.98△△ 12.07△△
B-MS 8 20.00±3.07**△△ 37.93△△
N-MS 8 35.13±4.54** 142.24
NCTD-lipiodol 8 22.86±2.59**△△ 57.76△△

Table 4

AI of liver tumor cells in rats after TACE in different groups（ヌ±S ）"

Group n AI
Normal saline 8 3.28±2.31**
NCTD 9 10.45±3.57**
B-MS 7 13.86±5.79**
N-MS 10 24.60±3.72
NCTD-lipiodol 7 16.60±4.86**

Figure 1

Apoptosis of liver tumor cells in rats in normal saline and N-MS groups after TACE (TUNEL staining, ×200)A: Normal saline group; B: N-MS group."

Table 5

Ki-67 expression level in livers tumor cells of rats after TACE in different groups （ヌ±S ）"

Group n Ki-67 LI (%)
Normal saline 8 62.23±6.65**
NCTD 9 40.33±5.47**
B-MS 7 35.00±4.43**
N-MS 10 12.06±4.62
NCTD-lipiodol 7 24.82±3.78**

Figure 2

Expression of Ki-67 in liver tumor cells of rats in normal saline and N-MS groups after TACE (SP staining, ×200)A: Normal saline group; B: N-MS group."

[1] 李琦, 凌昌全 . 原发性肝癌的介入治疗临床研究进展[J]. 临床消化病学杂志, 2001,13(2):94-96
[2] Alsowmely AM, Hodgson HJ . Non-surgical treatment of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2002,16(1):1-15
doi: 10.4103/1319-3767.151216
[3] Sakon M, Nagano H, Nakamori S , et al. Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics[J]. Arch Surg, 2002,137(1):94-99
[4] Kyotani S, Nishioka Y . The development of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma[J]. Yakugaku Zasshi, 2000,120(11):1173-1184
[5] Takeuchi I, Ishida H, Inokuma S , et al. Hepatic arterial injection of degradable starch microspheres(DSM) combined with adriamycin(ADM) and mitomycin C(MMC) in patients with liver metastasis of colorectal cancer[J]. Gan To Kagaku Ryohoi, 2000,27(12):1904-1906
[6] 李琦, 孟庆丽, 彭永海 , 等. 大鼠移植性肝癌模型的制作[J]. 第二军医大学学报, 2002,23(10):1074
doi: 10.3321/j.issn:0258-879X.2002.10.037
[7] 李琦, 刘晓华, 陈庆华 , 等. 蜂毒素微球经动脉介入治疗大鼠肝癌的实验研究[J]. 浙江中西医结合杂志, 2004,14(2):72-74
doi: 10.3969/j.issn.1005-4561.2004.02.003
[8] 韩克起, 顾伟, 胡侠 , 等. 小鼠肝癌原位移植模型的建立及生物学特征[J]. 中西医结合学报, 2004,2(5):372-374
[9] Minamimura T, Sato H, Kasaoka S , et al. Tumor regression by inductive hyperthermia combined with hepatic embolization using dextran magnetite-incorporated microspheres in rats[J]. Aint J Oncol, 2000,16(6):1153-1158
[10] 吴万根, 邓嵘, 区男全 , 等. 经肝动脉灌注莪术油微球对大鼠移植性肝癌的治疗作用[J]. 中华肝脏病杂志, 2000,8(1):24-26
doi: 10.3760/j.issn:1007-3418.2000.01.007
[11] Chan AO, Yuen MF, Hui CK , et al. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma[J]. Cancer, 2002,94(6):1747-1752
[12] Lo CM, Ngan H, Tso WK , et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma[J]. Hepatology, 2002,35(5):1164-1171
[13] Pohlen U, Berger G, Binnenhei M , et al. Increased carboplatin concentration in liver tumors through temporary flow retardation with starch microspheres(Spherex) and gelatin powder(Gelfoam): an experimental study in liver tumor-bearing rabbits[J]. J Surg Res, 2000,92(2):165-170
[14] Tamura T, Fujita F, Tanimoto M , et al. Anti-tumor effect of intraperitoneal administration of cisplatin-loaded microspheres to human tumor xenografted nude mice[J]. J Control Release, 2002,80(1-3):295-307
[15] Nijsen F, Rook D, Brandt C , et al. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study[J]. Eur J Nucl Med, 2001,28(6):743-749
[16] Kontogeorgos G . Classification and pathology of pituitary tumors[J]. Endocrine, 2005,28(1):27-35
doi: 10.1385/ENDO:28:1:027 pmid: 16311407
[1] Samuel Joshua Pragasam, Vachana Murunikara, Evan Prince Sabina, Mahaboobkhan Rasool. Antiperoxidative potential of p-coumaric acid, a common dietary phenol, in adjuvant-induced arthritis in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 932-938.
[2] Zi-hui Li, Jian Wang, Rong-lin Cai, You-wen Wang, Jian-peng Hu. Establishment and evaluation of a rat model of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency. Journal of Chinese Integrative Medicine, 2012, 10(8): 918-924.
[3] Dong-mei Zhang, Li-xia Lou, Ai-ming Wu, Xi-ying Lü, Zhao-juan Hu, Yan-hong Zhang, Hong-fang Liu. Effects of Astragalus membranaceus and Potentilla discolor mixture on insulin resistance and its related mRNA expressions in KKAy mice with type 2 diabetes. Journal of Chinese Integrative Medicine, 2012, 10(7): 821-826.
[4] Yan Guan , Hui Zhang, Wei Zhang, Shi-bing Su . Analysis of differential gene expression profile in peripheral blood of patients with chronic hepatitis B and syndromes of dual deficiency of liver and kidney yin and accumulation of dampness heat. Journal of Chinese Integrative Medicine, 2012, 10(7): 751-756.
[5] Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu . Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ. Journal of Chinese Integrative Medicine, 2012, 10(7): 793-799.
[6] Qing-bo Lang, Dong-xia Zhai , Feng Huang, Jian-guo Chen, Yong-hui Zhang, Qun Liu, Xiao-feng Zhai , Bai Li, Chang-quan Ling. Investigation on traditional Chinese medicine syndrome distribution of 4 618 hepatitis B virus infection subjects in Qidong of Jiangsu Province, China. Journal of Chinese Integrative Medicine, 2012, 10(5): 525-531.
[7] Li Weng, Juan Du, Wen-ring He, Chang-quan Ling. Characteristic genomics of peripheral blood mononuclear cells of hepatocellular carcinoma patients with liver-kidney yin deficiency syndrome. Journal of Chinese Integrative Medicine, 2012, 10(4): 406-415.
[8] Hui-jiao Liang , Zhen-jiao Liang , Xiao-ping Wang. Three-dimensional reconstruction of the Lung Meridian of Hand-Taiyin with continuous thin-section CT image. Journal of Chinese Integrative Medicine, 2012, 10(12): 1400-1404.
[9] Su-fang Zhang, Chang-quan Ling , Bai Li, Hong-yun Chen , Zhe Chen. Effects of Sisheng Decoction on the immunity and anti-stress function in mice with spleen deficiency syndrome. Journal of Chinese Integrative Medicine, 2012, 10(12): 1465-1469.
[10] Yan-qin Bian, Bing-bing Ning , Hong-yan Cao , Yan LU , Cheng Liu , Gao-feng Chen , Jia Liu , Ping Liu, Ming-yu Sun. Formula-syndrome correlation study of three classical anti-jaundice formulas in inhibition of liver fibrosis induced by dimethylnitrosamine in rats. Journal of Chinese Integrative Medicine, 2012, 10(12): 1405-1412.
[11] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271.
[12] Xiao Zhang , Bing-bing Ning , Shuang Ren , Li-jun Zhang , Wen-meng Zhang , Jia-mei Chen , Gao-feng Chen , Hua Zhang , Yong-ping Mu , Ping Liu. Effects of Chinese herbal medicine Xiaopi Pill in preventing rats from dimethylnitrosamine-induced liver fibrosis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1286-1292.
[13] Yuan-jie Wu , Zhao-hui Fang , Shu-guo Zheng , Yuan-bo Wu , Ai-hua Fan. Effects of Chinese herbal medicine Danzhi Jiangtang Capsule and exercise on JNK signaling pathway in pancreatic tissues of diabetic rats. Journal of Chinese Integrative Medicine, 2012, 10(11): 1279-1285.
[14] You-hua Wang , Shang Li , Bin-rui Yang , Lun-qing Zhang , Xin Zhou , Bei-wen Xu, Ming-yuan Li . Use of zebrafish models for the research of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1189-1197.
[15] Hui Han , Li-min Wu , Ming-xiang Han, Wen-ming Yang , Dao-jun Xie , Zhao-hui Fang , Dan-chen Chu , Fang Fang . Effects of Chinese herbal medicine Shenxiong Yujing Granule on regeneration of neural cells in rats with diabetes-associated cerebral ischemia. Journal of Chinese Integrative Medicine, 2012, 10(10): 1140-1148.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7] Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8] Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239
[an error occurred while processing this directive]