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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


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.


-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.


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.


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."

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