Antitumoral and Anti-inflammatory Roles of Somatostatin and Its Analogs in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and affects about 8% of cirrhotic patients, with a recurrence rate of over 50%. There are numerous therapies available for the treatment of HCC, depending on cancer staging and condition of the patient. The complexity of the treatment is also justified by the unique pathogenesis of HCC that involves intricate processes such as chronic inflammation, fibrosis, and multiple molecular carcinogenesis events. During the last three decades, multiple in vivo and in vitro experiments have used somatostatin and its analogs (SSAs) to reduce the proliferative and metastatic potential of hepatoma cells by inducing their apoptosis and reducing angiogenesis and the inflammatory component of HCC. Most experiments have proven successful, revealing several different pathways and mechanisms corresponding to the aforementioned functions. Moreover, a correlation between specific effects and expression of somatostatin receptors (SSTRs) was observed in the studied cells. Clinical trials have tested either somatostatin or an analog, alone or in combination with other drugs, to explore the potential effects on HCC patients, in various stages of the disease. While the majority of these clinical trials exhibited minor to moderate success, some other studies were inconclusive or even reported negative outcomes. A complete evaluation of the efficacy of somatostatin and SSAs is still the matter of intense debate, and, if deemed useful, these substances may play a beneficial role in the management of HCC patients.

Octreotide attenuates intestinal barrier damage by maintaining basal autophagy in Caco2 cells

“…In addition, results of a previous study demonstrated that OCT may be used to effectively treat patients with thymic epithelial tumors expressing SSTR2 ( 50 ). Somatostatins are used for the inhibition of inflammatory responses in clinical practice ( 51 ). Of note, the 2A subtype of SSTRs is used in the treatment of IBD, and the regulation of nerve transmission, proliferation and apoptosis ( 46 ).…”

The State-of-the-Art Mechanisms and Antitumor Effects of Somatostatin in Colorectal Cancer: A Review

“…SSAs are used as monotherapy or in combination with other forms of therapy. However, treatment effects are highly variable, and the antitumor role of SSTs in these cancers is still unclear [ 22 , 270 ].…”

“…HCC is the most common primary liver cancer and better treatments are still being sought due to high recurrence rates (>50%), even after aggressive therapies [ 270 ]. Differential expression of SSTRs was confirmed in selected HCC cell lines (e.g., SMMC-7721, HepG2 and BEL-7402), normal liver cells (L-02) [ 299 ] and in HCC tissues in vivo [ 300 , 301 ].…”

“…Several randomized trials with this type of SSA have been performed, lasting from several months to 5 years. Very different results were obtained [ 270 ]. Examples of randomized trials show both an extension of the average survival time of patients after using OCT and a decrease in AFP concentration [ 301 , 305 ], as well as a lack of impact of this SSA on life extension, tumor regression or changes in AFP concentration in advanced HCC [ 300 ].…”

“…However, the use of transarterial chemoembolization (TACE) with celecoxib and LAM prolonged OS, increased tumor response, reduced post-embolization syndrome and was well tolerated by patients with unresectable HCC [ 311 ]. The role of SSAs based on in vitro and in vivo studies, as well as the use of various SSA preparations in patients with HCC, is described in detail in the latest review [ 270 ].…”