Carcinogenesis, Teratogenesis & Mutagenesis ›› 2018, Vol. 30 ›› Issue (6): 435-441.doi: 10.3969/j.issn.1004-616x.2018.06.004

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Inhibitory effect of total alkaloids of Tougucao on bone metastasis of breast cancer cells in mice

DU Juan1, HU Xiangyang2, LIU Dan1, HU Wei1, CHEN Tao1   

  1. 1. China Three Gorges University School of Medicine, Yichang 443002;
    2. The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, Hubei, China
  • Received:2018-07-27 Revised:2018-09-10 Online:2018-11-30 Published:2018-11-30

Abstract: OBJECTIVE: To explore the inhibitory effect of the total alkaloids of Tougucao (TTAT) on bone metastasis of breast cancer cells in mice and to investigate the mechanisms. METHODS: Alkaloids contained in the extract was identified by chromogenic reaction. Female nude mice were randomly divided into 6 groups of 7 each:normal (routine feeding),model (only modeling),TTAT low concentration (100 mg/kg TTAT intraperitoneal injection),TTAT high concentration (500 mg/kg TTAT intraperitoneal injection),DOX (5 mg/kg DOX intraperitoneal injection),and ZOL group (0.4 mg/kg ZOL subcutaneous injection after neck). The human breast cancer MDA-MB-231 cells were injected into the tibia to establish the bone metastasis model of breast cancer. The other groups were administered the drugs once every other day for 6 weeks after tumor formation except the normal and the model groups. During the administration,the body weight and tumor volume of each group were measured regularly and the living activities of each group were observed closely. At the end of the experiment,all the nude mice were killed by cervical dislocations,and the right hind limbs were removed at the right hip joint. Imaging,HE staining and TRAP staining were used to observe and evaluate the effect of TTAT on the growth of tibia and tumor tissues of nude mice with tibial bone metastases from breast cancer. The effects of TTAT on the RANKL/OPG ratio and the expression of p-ERK,ERK,p-JNK and JNK in the tumor tissue of the tibial bone metastases of breast cancer were detected by Western blot. RESULTS: 3.28 g was extracted from Tougucao and three alkaloid chromogenic reagents showed positive results,indicating the presence of alkaloids. Compared with the model group,the quality of tumor in the TTAT group decreased significantly (P < 0.01) while imaging scores increased (P < 0.01). The HE staining showed that TTAT significantly inhibited the formation of tumor nests,reduced the nuclear division and protected metastases to the tibia. The TRAP staining results showed that the number of osteoclasts in the TTAT group decreased significantly (P < 0.05). Western blot results showed that TTAT significantly reduced the RANKL/OPG ratio in the tumor tissue of the tibial bone metastases (P < 0.05),and reduced the expression of p-ERK and p-JNK (P < 0.05). CONCLUSION: TTAT significantly inhibited the growth and tibial bone metastasis of breast cancer. The observed effect could be mediated via the OPG/RANK/RANKL signaling pathway.

Key words: Tougucao, alkaloids, breast cancer, bone metastases, NF-kappa B receptor activator ligand

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