Experimental Studies On Anti-tumor Effect And Toxicity Of Cucurbitacin Liposome For Injection

This paper focused on the anti-tumor activity in vivo and in vitro and toxicity of CucurbitacinLiposome for Injection (CLI).The inhibitory effects of CLI on tumor growth were observed by using the models ofimplanted hepatoma 22 (H₂₂ ),sarcoma 180 (S₁₈₀ ) and Lewis lung carcinoma in mice. The resultsshowed CLI (27．5,55,110μg·kg^-1 ) inhibited obviously the growth of the three kinds of tumorsin mice. Inhibitory effect of CLI combination with cyclophosphamid (CTX) or 5-fiuorouracil(5-FU) on H₂₂ hepatic carcinoma in mice was also studied. The results showed that the tumorweights in animals treated by CLI combination with CTX or 5-FU were decreased significantlycompared with that treated with CTX or 5-FU alone, and CLI could increase the number ofperipheral blood leucocyte in mice bearing H₂₂ hepatocellular carcinoma. In the animal modelsof immunodepression induced by CTX, the spleen index, thymus index and the clearance rate ofcharcoal particles were measured. CLI increased significantly the spleen index, thymus indexand the clearance rate of charcoal particles. CLI could reinforce the immunological function oflow-immune mice treated with CTX.The inhibitory effects of CLI on proliferation of human cervical carcinoma cell lines HeLa,human hepatocarcinoma cell lines BEL-7402, human hepatocarcinoma cell lines HepG2 andmurine S₁₈₀ cell lines were measured by MTT colorimetric assay or trypan blue assay in vitro.The results showed CLI possessed the antiproliferative activity against different tumor lines in adose-dependent manner. Flow cytometric analysis showed that CLI treatment arrested cell cycleat G2/M phase in S₁₈₀ cells. Therefore, we presume that G2/M arrest of cell cycle may beinvolved in the growth inhibitory effect by CLI.Experimental studies on the toxicity of CLI were performed according to the guidelines of theSFDA. Acute toxicity test showed that the half lethal dose (LD₅₀ ) of CLI in mice was 1．29 mg·kg^-1 by intravenous administration and 1．39 mg·kg^-1 by intraperitoneal administration,respectively. In general pharmacology research, the results showed that CLI had no markedimpact on the nervous system, respiratory system and the cardiovascular system. In the activecutaneous anaphylaxis and passive cutaneous anaphylaxis test, no evident allergic effect inducedby CLI in the animals was observed. Chronic toxicity test showed that: (1) in rats, the toxictarget organs were liver, spleen and kidney, and the non-toxic dose of CLI was 0．09 mg·kg^-1 . (2) in Beagle dogs, the toxic target organs were liver and kidney, and the non-toxic dose of CLI was0．03 mg·kg^-1 .