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Effects of Macrothele raven venom on intrarenal invasion and metastasis of H22 liver cancer cells in mice

Yi Hou, Xiaokun Zhao, Jiaqin Chen, Jingsheng Zhou, Weiwei Chen, Haifeng Mao, Rui Chen
Published: 1 January 2017
 by  Medknow

Abstract: Background: Extrahepatic metastatic hepatocellular carcinoma (HCC) and its insensitivity to chemotherapy are the main causes of poor prognosis in patients with HCC. This study investigated the anti-cancer effect of Macrothele raveni venom on intrarenal metastatic HCC. Materials and Methods: Subrenal capsule xenograft model of HCC was established by inoculation of H22 liver cancer cells. Results: The general health, histology, and molecular changes were observed after administering 10 times of different dose of Macrothele raven venom injections. A volume of 0.8 μg/ml and 1.0 μg/ml of Macrothele raven venom significantly improved general health status in mice with subrenal capsule HCC tumors. Hematoxylin and eosin staining showed that Macrothele raven venom dose-dependently reduced invasion and metastasis of liver cancer cells in the kidney. Immunohistochemistry and real-time polymerase chain reaction showed that Macrothele raven venom injection dose-dependently decreased PI3K mRNA and protein, Akt protein, and mTOR mRNA expression, but increased Bad mRNA and protein expression in the kidney with H22 tumor cell invasion. 0.8 μg/ml is the most effective dose for the treatment of intrarenal metastatic HCC. Conclusions: Macrothele raven venom dose-dependently inhibits invasion and metastasis of intrarenal metastatic HCC through inhibition of PI3K-Akt-mTOR signaling and increase of Bad expression.
Keywords: Akt / Bad / extrahepatic metastasis / hepatocellular carcinoma / invasion / Macrothele raven venom / mTOR / PI3K

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