[Effects of interstitial chemotherapy using thermosensitive gel-coated ricin on hepatoma H22-bearing mice].
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).


CONCLUSIONS
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.
Department of Ultrasonics, Union Hospital, and Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350001, Fujian Province, China.
Zhi-kui
ZK
Chen
Li-wu
LW
Lin
Fa-duan
FD
Yang
Xiu-hua
XH
Weng
Hua-jing
HJ
Cai
En-sheng
ES
Xue
Yan
Y
Wang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D053148:Caspase 3 / Q000378:metabolism; D004337:Drug Carriers; D020100:Hydrogels; D015552:Injections, Intralesional; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D012276:Ricin / Q000008:administration & dosage*
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D020100:Hydrogels; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D012276:Ricin; C505409:Casp3 protein, mouse; D053148:Caspase 3