[Inhibitory effect of emodin on the growth of cervical cancer in tumor-transplanted mice and underlying mechanism].
OBJECTIVE
To observe the effect of emodin on the growth of transplanted U14 cervical cancer cells in mice, and explore its mechanism of anti-tumor.


METHODS
The 615-strain mice with U14 cervical cancer cells were randomly divided into 4 groups: control group (DMSO), low-dose emodin group (20 mg/kg), high-dose emodin group (40 mg/kg) and cisplatin group (3 mg/kg). Each group included 10 mice. After drug intervention, all mice were sacrificed on day 26 posttransplantation. The volumes and mass of tumors were detected, and tumor inhibition rate was calculated. Microvessel density (MVD) was determined by immunohistochemistry. The mRNA and protein levels of hypoxia inducible factor-1α (HIF-1α), vascular endothelia growth factor (VEGF) and macrophage migration inhibitory factor (MIF) in tumor tissues were analyzed by real-time quantitative PCR and Western blotting, respectively. Apoptosis index (AI) of tumor tissues was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the Bcl-2 and Bax protein contents were detected by Western blotting.


RESULTS
The tumor inhibition rates were 15.83%, 46.92% and 51.22% in low-dose emodin group, high-dose emodin group and cisplatin group, respectively. The tumor inhibition rates were higher in the latter two groups than that in low-dose emodin group. In comparison with control group and low-dose emodin group, the volumes and mass of tumor, MVD as well as the level of HIF-1α, VEGF, MIF and Bcl-2 significantly decreased, while the level of AI and Bax significantly increased in high-dose emodin group and cisplatin group. Low-dose emodin had no effects on the above parameters.


CONCLUSIONS
Emodin might suppress the growth of cervical cancer in mice by reducing tumor neovascularization, decreasing MIF expression and promoting tumor cell apoptosis.
Department of Obstetrics and Gynecology, First Affiliated Hospital, University of South China, Hengyang 421001, China.
Jing
J
Zhang
Department of Oncological Surgery, First Affiliated Hospital, University of South China, Hengyang 421001, China.
Zecheng
Z
Hu
Department of Obstetrics and Gynecology, First Affiliated Hospital, University of South China, Hengyang 421001, China.
Zhongdong
Z
Chen
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004642:Emodin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D004642:Emodin