Hou Yi, Zhao Xiaokun, Chen Jiaqin, Zhou Jingsheng, Chen Weiwei, Mao Haifeng, Chen Rui
Department of Urological Surgery, Second Xiangya Hospital, Central South University, Changsha 410012, PR China.
Physical Education College, Hunan Normal University, Changsha 410012, PR China.
J Cancer Res Ther. 2017;13(4):725-729. doi: 10.4103/jcrt.JCRT_1286_16.
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.
Subrenal capsule xenograft model of HCC was established by inoculation of H22 liver cancer cells.
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.
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.
肝外转移性肝细胞癌（HCC）及其对化疗的不敏感性是HCC患者预后不良的主要原因。本研究探讨了雷氏大疣蛛毒液对肾内转移性HCC的抗癌作用。
通过接种H22肝癌细胞建立HCC肾被膜下移植瘤模型。
给予不同剂量雷氏大疣蛛毒液注射10次后，观察一般健康状况、组织学和分子变化。0.8μg/ml和1.0μg/ml的雷氏大疣蛛毒液显著改善了肾被膜下HCC肿瘤小鼠的一般健康状况。苏木精-伊红染色显示，雷氏大疣蛛毒液剂量依赖性地降低了肝癌细胞在肾脏中的侵袭和转移。免疫组织化学和实时聚合酶链反应显示，注射雷氏大疣蛛毒液剂量依赖性地降低了PI3K mRNA和蛋白、Akt蛋白以及mTOR mRNA的表达，但增加了H22肿瘤细胞侵袭的肾脏中Bad mRNA和蛋白的表达。0.8μg/ml是治疗肾内转移性HCC的最有效剂量。
雷氏大疣蛛毒液通过抑制PI3K-Akt-mTOR信号通路和增加Bad表达，剂量依赖性地抑制肾内转移性HCC的侵袭和转移。
