Abstract
Milciclib and sorafenib synergistically downregulate c-Myc to suppress tumor growth in an orthotopic murine model of human hepatocellular carcinoma
Highlights
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of cancer-related deaths worldwide [1,2]
A set of experiments were conducted to determine IC50 values of milciclib, sorafenib, lenvatinib and regorafenib to inhibit proliferation, induce apoptosis and to delay wound healing in HepG2.215, MHCC97-H and MHCC97-L cells, which were derived from a patient with metastatic HCC [24]
We evaluated the effects of milciclib, sorafenib, lenvatinib and regorafenib either as single agent or in combination on proliferation, apoptosis and cytotoxicity using ApoTox-Glo Triplex assay (Promega)
Summary
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of cancer-related deaths worldwide [1,2]. Chronic liver inflammation resulting from prolonged viral hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and other metabolic disorders such as excessive alcohol consumption and exposure to aflatoxins represent major etiological factors for HCC [1,2,3]. Immunotherapies with nivolumab (Opdivo®) and pembrolizumab (Keytruda®) both inhibiting programmed cell death receptor PD-1, have been approved as second line treatment for advanced HCC [10,11]. These therapies have shown significant clinical benefits for HCC patients, but the clinical response rate is still low. There is an immediate need for drugs, preferentially with different mechanisms, which could be used in suitable combinations to complement existing therapies and to improve clinical outcome without compromising safety
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