Abstract
BackgroundHepatocellular carcinoma (HCC) is the most prevalent hepatic cancer worldwide. Currently, a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is undergoing continual development in HCC treatment.MethodsIn this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific antigens from both membrane and cytoplasmic fractions of HepG2 cell line were identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E. coli BL21(DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1–3 days was investigated using a transmission electron microscope.ResultsThe result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) and alpha-enolase. In addition, the gradual appearing of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Those characteristics might be explained by the paraptosis-like program cell death (PCD), which is induced by the binding of Hep88 mAb to mortalin (HSPA9). Mortalin depletion resulting from the formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independence of p53-mediated apoptosis. Additionally, Hep88mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction.ConclusionThese fascinating results imply that Hep88 mAb might be a promising tool for the development of an effective treatment of HCC in the next decade.
Highlights
Hepatocellular carcinoma (HCC) is the most prevalent hepatic cancer worldwide
A targeted therapy such as the immunotherapy via monoclonal antibodies specific to tumor-associated antigen has become a fascinating tool for the targeting of specific HCC cells that are critical to tumor progression while reducing toxicity to normal cells [18,19,20]
The possible mechanisms of anti-tumor effect of monoclonal antibodies (mAbs) might be involved in blocking the growth-factors receptor, inducing apoptosis or activating complement cascade resulting in tumor cell lysis and phagocytosis by macrophage [21,22,23]
Summary
A targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is undergoing continual development in HCC treatment. Its prevalence and mortality rate varies from region to region, and is noticeably lower in most developed areas (5–10 per 100,000), but is detected to Currently, technologies in treatment of the HCC are being continuously developed and include hepatic resection and those of non-surgical management, i.e. percutaneous ethanol injection: PEI [12], transcatheter oily chemoembolization: TOCE [13], radiofrequency ablation (RFA) [14]. The survival rates depend on many factors, but especially on tumor size and staging [15,16,17] This trend is being caused by a lack of sensitive and specific early detection, and effective treatment for the cure of any remaining cancer cells. The possible mechanisms of anti-tumor effect of mAbs might be involved in blocking the growth-factors receptor, inducing apoptosis or activating complement cascade resulting in tumor cell lysis and phagocytosis by macrophage [21,22,23]
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