Effects of angiotensin ii type 2 receptor overexpression on the growth of hepatocellular carcinoma cells in-vitro and in-vivo
Answers
Hepatocellular carcinoma (HCC) is one of the most common human cancers worldwide and the third most common cause of cancer-related deaths. More than 80% of HCC cases originate in developing countries ]. Diagnosis of advanced stage of HCC is a devastating experience for both patients and family. HCC is often diagnosed at an advanced stage when it is no longer susceptible to curative therapies. Moreover, the highly drug-metabolic and multidrug resistant transporter proteins in tumor cells further diminish the efficacy of current therapeutic regimens for HCC Therefore, alternative approaches are needed to overcome these barriers to enhance therapeutic efficacy.
Gene therapy is a promising treatment for many hereditary diseases such as Leber’s congenital amaurosis, X-linked adrenoleukodystrophy and ‘bubble boy’ disease, and was selected as one of the top 10 breakthroughs of 2009 by the editors of Science. As a major gene therapy milestone, the European Union has recently approved the sale of the Western world’s first gene-therapy drug, Glybera, to treat patients with lipoprotein lipase deficiency [3]. Thus far, most of the clinical trials in gene therapy have been aimed at the treatment of cancer (64.4% of all gene therapy trials). Many different cancers have been targeted throughout the years, including lung, gynaecological, skin, urological, neurological and gastrointestinal tumors, as well as haematological malignancies and paediatric tumors However, there are currently no approved gene therapy products for cancer in the Western world. Identification of functionally relevant tumor-specific genes for therapeutic targets remains as the major challenge in cancer gene therapy.
Angiotensin II (Ang II), the key effector in the renin-angiotensin system, acts through two well-defined receptors: Ang II type 1 (AT1R) and type 2 receptors (AT2R) [5]. Recent studies suggest that Ang II signaling plays an important role in carcinogenesis [6]–[8]. Using a murine hepatocellular carcinoma development model, Yoshiji and colleagues [9]–[11] showed that combination therapy based on an angiotensin-converting enzyme (ACE) inhibitor (Perindopril [PE]) was able to inhibit angiogenesis mediated by VEGF overexpression. AT2R is known to inhibit cell proliferation and stimulate apoptosis in a variety of cell lines, such as vascular smooth muscle cells, cardiomyocytes, neuronal cells, fibroblasts, endothelial cells, prostate cancer cells and lung cancer cells, but the role of AT2R in HCC progression is currently unclear [12]–[21]. Here we have confirmed the inhibitory effects of adenoviral-induced AT2R overexpression on proliferation and apoptosis of hepatocellular carcinoma cells and have addressed the potential intracellular mechanisms. We have further studied the effects of AT2R on tumor growth in mouse models of the human HCC.
Explanation:
Carcinoma is a type of cancer that starts in cells that make up the skin or the tissue lining organs, such as the liver or kidneys. Like other types of cancer, carcinomas are abnormal cells that divide without control. They are able to spread to other parts of the body, but don't always.