Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model
Dongbin Bi, Mingshan Yang, Xia Zhao, Shiming Huang
Department of Urology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland)
Med Sci Monit 2015; 21:2421-2427
Cnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis.
MATERIAL AND METHODS: We randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/Kg), and cnidium lactone groups at 3 doses (280 mg/Kg, 140 mg/Kg, and 70 mg/Kg). The mice were weighed at 2 weeks after administration. Tunnel assay was applied to test the nude mice tumor cell apoptosis. ELISA was performed to detect serum AMACR, CD147, mutant P53, BCL-2, AND BAX expression levels. Tumor tissue was separated and weighed.
RESULTS: Mice weight did not change significantly in the groups receiving 3 different doses of cnidium lactone(p>0.05), while it decreased obviously in the cyclophosphamide group (p<0.05). Tumor weight, CD147, mutant P53, and BCL-2 levels were significantly lower in the groups receiving 3 different doses of cnidium lactone than in the negative control group (p<0.05). Among them, the abovementioned indexes decreased markedly in the 280 mg/Kg and 140 mg/Kg dose groups than in the cyclophosphamide group (p<0.05). AMACR and BAX levels showed no significant difference in the cnidium lactone group or the cyclophosphamide group (p>0.05).
CONCLUSIONS: Cnidium lactone may induce prostate cancer cell apoptosis and inhibit its proliferation through regulating CD147, mutant P53, and BCL-2 expression in nude mice.
Keywords: Antigens, CD147 - blood, Animals, Antineoplastic Agents, Phytogenic - pharmacology, Apoptosis - drug effects, Biomarkers, Tumor - genetics, Cell Line, Tumor, Cnidium - chemistry, Coumarins - pharmacology, Cyclophosphamide - pharmacology, Lactones - pharmacology, Mice, Mice, Inbred BALB C, Mice, Nude, Mutant Proteins - genetics, Prostatic Neoplasms - genetics, Proto-Oncogene Proteins c-bcl-2 - blood, Racemases and Epimerases - blood, Tumor Suppressor Protein p53 - genetics, Xenograft Model Antitumor Assays, bcl-2-Associated X Protein - blood