Search JIM Advanced Search

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

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] Xuanbin Wang, Ning Wang, Fan Cheung, Lixing Lao, Charlie Li, Yibin Feng. Chinese medicines for prevention and treatment of human hepatocellular carcinoma: Current progress on pharmacological actions and mechanisms. Journal of Integrative Medicine, 2015, 13(3): 142-164.
[2] 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.
[3] 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.
[4] 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.
[5] Cai Lin-lin, Li Hao, Liu Jian-gang, Liu Long-tao, Guan Jie, Liu Ming-fang, Hu Jia, Wei Yun. Effects of early intervention with Huannao Yicong formula effective components on behavior and cholinergic system of β-amyloid precursor protein transgenic mice. Journal of Chinese Integrative Medicine, 2011, 9(3): 292-298.
[6] Xiao-bing Li, Xiao-juan He, Biao Liu, Li Xu, Da-hong Ju, Miao Jiang, Ai-ping Lu. Immunoregulatory function of Radix Glycyrrhizae polysaccharide in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2010, 8(4): 363-367.
[7] Yan Wang , Li-wu Lin, Zhi-kui Chen, En-sheng Xue, Xiao-dong Lin, Li-yun Yu, Zhen-hu Lin. Effects of intratumoral injection of microspheres containing cobra venom cytotoxin on transplanted human hepatoma in nude mice. Journal of Chinese Integrative Medicine, 2009, 7(9): 836-841.
[8] Zhi-kui Chen, Li-wu Lin, Fa-duan Yang, Xiu-hua Weng, Hua-jing Cai, En-sheng Xue, Yan Wang. Effects of interstitial chemotherapy using thermosensitive gel-coated ricin on hepatoma H22-bearing mice. Journal of Chinese Integrative Medicine, 2009, 7(5): 447-452.
[9] Yong-jun Wang, Qi Shi, Jian-chun Jiang, Qian-qian Liang, Qin Bian, Chen-guang Li, Quan Zhou, Xue-jun Cui, Min Huang, Qing-gao Liu, Sheng Lu, Chong-jian Zhou. Establishment of a rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency. Journal of Chinese Integrative Medicine, 2008, 6(11): 1152-1158.
[10] Wei Gu, Ke-qi Han, Yong-hua Su, Xue-qiang Huang, Chang-quan Ling. Inhibition action of bufalin on human transplanted hepatocellular tumor and its effects on expressions of Bcl-2 and Bax proteins in nude mice. Journal of Chinese Integrative Medicine, 2007, 5(2): 155-159.
[11] Xiao-qiang Yue​, Jing-dong Gao​, Xiao-feng Zhai​, Qing Liu​, Dong Jiang​, Chang-Quan Ling. Correlation between the width of lingual vein and the changes of hemodynamics of portal system in patients with primary liver cancer. Journal of Chinese Integrative Medicine, 2006, 4(5): 482-484.
[12] Wei-zhe Deng, Xiao-qiang Yue, Qing Liu, Jing-dong Gao, Rong-zheng Ren, Chang-quan Ling. Comparative study on normal tongue manifestation in patients with primary liver cancer and healthy adults. Journal of Chinese Integrative Medicine, 2006, 4(1): 13-16.
[13] Yue-lai Chen, Jue Cen, Wen-guang Hou, Zhi-qiang Gao, Xian-min Yu, Xue-mei Ma. Effects of electroacupuncture treatment on nitrergic neurotransmitter in bladder neck and detrusor of rats with unstable bladder. Journal of Chinese Integrative Medicine, 2006, 4(1): 73-75.
[14] Li-xia Ju, Zhe Chen, Rong-zheng Ren. Progress in research on the treatment of primary liver cancer with traditional Chinese medicine for activating blood to resolve stasis. Journal of Chinese Integrative Medicine, 2005, 3(6): 491-494.
[15] Qing Liu, Yan-bo Zhang, Chuan-hong Ma, Xiao-qiang Yue, Chang-quan Ling. Analysis of literature on therapeutic methods and medicines of traditional Chinese medicine for primary liver cancer. Journal of Chinese Integrative Medicine, 2005, 3(4): 260-262.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 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
[2] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[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] 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
[5] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[6] Bing Hu , Hong-mei An , Ke-ping Shen , Qin Du. Senescence-inducing effects of Chinese herbal medicine Tenglong Buzhong Decoction on human colon carcinoma LS-174-T cells and the mechanism. Journal of Chinese Integrative Medicine, 2010, 8(11): 1048-1052
[7] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[8] Liang-ping Hu, Xiao-lei Bao. Three-factor designs unable to examine the interactions (Part 2). Journal of Chinese Integrative Medicine, 2012, 10(11): 1229-1232
[9] Nian-hong Wang , Jun-tao Yan , Wu-quan Sun , Yong-shan Hu , Jun Xia , Li-cheng Wei , Jie Jia , Gui-lin Ouyang , Yong He , Yan-ming Guo , Jie Xu . Effects of early application of Tuina treatment on quadriceps surface myoelectricity in patients after total knee arthroplasty: a randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(11): 1247-1253
[10] Kishan Lal Tiwari, Shailesh Kumar Jadhav, Veenu Joshi. An updated review on medicinal herb genus Spilanthes. Journal of Chinese Integrative Medicine, 2011, 9(11): 1170-1178