Oncolytic Adenovirus-Mediated E1A Gene Therapy Induces Tumor-Cell Apoptosis and Reduces Tumor Angiogenesis Leading to Inhibition of Hepatocellular Carcinoma Growth in Animal Model

Cortex periplocae is the dried root bark ofPeriploca sepiumBge., a traditional Chinese herb medicine. It contains high amounts of cardiac glycosides. Several cardiac glycosides have been reported to inhibit tumor growth or induce tumor cell apoptosis. We extracted and purified cortex periplocae and identified periplocin as the active ingredient that inhibited the growth of TNF-related apoptosis-inducing ligand-(TRAIL-) resistant hepatocellular carcinoma cells. The antitumor activity of periplocin was further increased by TRAIL cotreatment. Periplocin sensitized TRAIL-resistant HCC through the following two mechanisms. First, periplocin induced the expression of DR4 and FADD. Second, the cotreatment of TRAIL and periplocin suppressed several inhibitors of apoptosis (IAPs). Both mechanisms resulted in the activation of caspase 3, 8, and 9 and led to cell apoptosis. In addition, intraperitoneal injection (IP) of periplocin repressed the growth of hepatocellular carcinoma (HCC) in xenograft tumor model in mice. In summary, periplocin sensitized TRAIL-resistant HCC cells to TRAIL treatment and resulted in tumor cell apoptosis and the repression of tumor growthin vivo.

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Induction of Tumor Cell Apoptosis by TRAIL Gene Therapy

Gene Therapy of Cancer - Methods in Molecular Biology™ ◽

10.1007/978-1-59745-561-9_17 ◽

2009 ◽

pp. 315-334 ◽

Cited By ~ 4

Author(s):

Thomas S. Griffith

Keyword(s):

Gene Therapy ◽

Tumor Cell ◽

Cell Apoptosis ◽

Tumor Cell Apoptosis

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Jianpi-Huayu Formula Inhibits Development of Hepatocellular Carcinoma by Regulating Expression of miR-602, Which Targets the RASSF1A Gene

Integrative Cancer Therapies ◽

10.1177/1534735419900804 ◽

2020 ◽

Vol 19 ◽

pp. 153473541990080 ◽

Cited By ~ 1

Author(s):

Yajing Huang ◽

Cheng Zhou ◽

Huihong Wen ◽

Yongxu Chen ◽

Yingjie Xie ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Protein Expression ◽

Tumor Cell ◽

Liver Tumor ◽

Cell Apoptosis ◽

Control Group ◽

Tumor Cell Apoptosis ◽

Expression Levels ◽

Rassf1a Gene ◽

Tumor Tissues

The traditional Chinese medicine formula Jianpi-Huayu (JPHY) has been reported to be effective in the treatment of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. In this article, we employed an orthotopic transplantation model in nude mice to explore whether JPHY could inhibit the development of HCC by regulating miR-602, which targets the Ras association domain-containing protein 1A (RASSF1A) pathway. HCC SMMC-7721 cells were treated with JPHY to test whether the RASSF1A gene as mediated by miR-602 affected the proliferation and apoptosis of tumor cells. We subsequently detected miR-602, RASSF1A, and tumor cell apoptosis–related markers in cells and liver tumor tissues. We observed that mice treated with JPHY had smaller tumors and higher survival rates than untreated ones. Similarly, JPHY-treated SMMC-7721 cells exhibited alterations in morphology and higher cytotoxicity compared with the control group. Furthermore, we found that JPHY decreased overexpression of miR-602 and increased protein expression levels of the RASS1A gene, which in turn altered protein expression levels of tumor cell apoptosis–related genes in the cells and liver tumor tissues of drug-treated mice. These results indicated that JPHY could potentially be used to treat HCC by targeting miR-602, which targets the RASSF1A gene, which in turn plays a major role in HCC pathogenesis.

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