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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (5): 447-452.doi: 10.3736/jcim20090509

• Original Experimental Research • Previous Articles     Next Articles

Effects of interstitial chemotherapy using thermosensitive gel-coated ricin on hepatoma H22-bearing mice

Zhi-kui Chena,Li-wu Lina,Fa-duan Yangb,Xiu-hua Wengc,CAI Hua-jingd,XUE En-shenga,WANG Yana   

  1. a Department of Ultrasonics, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
    b Department of Pathology, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
    c Department of Pharmacy, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
    d Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350001, Fujian Province, China
  • Received:2008-11-10 Accepted:2009-02-04 Online:2009-05-20 Published:2018-10-15

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Objective

To explore the efficacy and feasibility of interstitial chemotherapy using thermosensitive gel-coated ricin in hepatoma H22-bearing mice.
Methods

Ricin was purified by chromatography method. The purified ricin was identified by Western blot assay and the purity was determined by high-performance liquid chromatography. BALB/c mice were inoculated subcutaneously in right flank with hepatoma H22 cells. When the tumor size reached about 1.0 cm in diameter, 40 mice were randomly divided into untreated group, thermosensitive gel group, ricin group and thermosensitive gel-coated ricin group. Mice in each group were administered different agents by percutaneous intratumoral injection, including normal saline, thermosensitive hydrogel, ricin and thermosensitive gel-coated ricin. Fifteen days after treatment, the tumors were removed to calculate inhibition rate of tumor growth. The tumor tissues were made into pathological sections to perform histopathological examination. The ultrastructure of tumor tissue was examined by electron microscope examination as well. Blood was collected to detect the hepatic and renal functions. The caspase-3 activity of tumor tissue was determined by using zymologic method with a spectrophotometer.
Results

After intratumoral therapy, tumor weight in the thermosensitive gel-coated ricin group was lower than that in the untreated group, with a tumor growth inhibition rate of 71.31%. No obvious hepatic or renal toxicities were detected after thermosensitive gel-coated ricin treatment. Histopathologic observation of the tumor tissue showed massive necrosis and typical apoptosis phenomena, including chromatin margination and apoptotic body. Meanwhile, thermosensitive gel-coated ricin resulted in a significant increase in the caspase-3 activity as compared with the untreated group and the ricin group (P<0.01, P<0.05).
Conclusion

The above findings indicate that intratumoral therapy with thermosensitive gel-coated ricin has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.

Key words: Ricin, Liver neoplasms, Drug therapy, Administration, Topical, Delayed-action preparations, Mice

Figure 1

Determination of ricin purity by high performance liquid chromatography"

Figure 2

Identification of ricin by Western blot assay"

Figure 3

Phase diagram of PLGA-PEG-PLGA copolymer aqueous solutions With increasing of the copolymer concentration from 15% to 30% (weight fraction), the gelation temperature decreases from 28.5 ℃ to 22.5 ℃."

Table 1

Effects of interstitial chemotherapy on tumor growth in different groups"

Group n Tumor weight (x±s, g) Inhibition rate (%)
Untreated 10 2.13±0.41
Thermosensitive gel 10 2.04±0.43 4.25
Ricin 10 1.42±0.28* 33.33
Thermosensitive gel-coated ricin 10 0.61±0.19**△ 71.31

Table 2

Effects of interstitial chemotherapy on hepatic and renal functions in different groups（x±s）"

Group n ALT (U/L) AST (U/L) Bun (mmol/L) Cr (μmol/L)
Untreated 10 35.12±6.85 112.36±21.01 11.62±1.69 67.25±9.26
Thermosensitive gel 10 39.45±7.23 106.85±23.52 13.02±1.95 70.52±10.52
Ricin 10 52.59±8.16* 168.54±29.74* 12.89±1.94 71.54±10.96
Thermosensitive gel-coated ricin 10 39.25±6.98 128.68±29.74 10.22±1.39 69.75±9.56

Figure 4

Histopathologic changes of tumor tissues observed by light microscope (HE staining, ×200) A: Untreated group; B: Thermosensitive gel group; C: Ricin group; D: Thermosensitive gel-coated ricin group."

Figure 5

Ultrastructure changes of tumor tissues (Transmission electron microscopy, ×5 000) A: Untreated group; B: Thermosensitive gel group; C: Ricin group; D: Thermosensitive gel-coated ricin group."

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