Effects of Macrothele raven venom on intrarenal invasion and metastasis of H22 liver cancer cells in mice
Journal of Cancer Research and Therapeutics , Volume 13, pp 725-729; https://doi.org/10.4103/jcrt.JCRT_1286_16
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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