Surprise! Statins against liver cancer help develop new liver cancer drugs

Hepatocellular carcinoma (HCC) is a common primary liver malignancy, accounting for more than 80% of primary liver cancer.
, liver cancer is the fifth and seventh most common cancer among men and women, respectively, and the third and sixth most common causes of cancer-related death.
the mortality rate of hepatocellular carcinoma is almost the same as that of morbidity due to poor prognosis.
, liver cancer patients are usually diagnosed in advanced stages, which means that some treatments (e.g. surgical removal, liver transplantation) are only available in a small number of patients.
currently, only sorafenib and regorafenib, the FDA-approved first-line treatments for liver cancer, extend the medium lifetime by only 10-12 weeks.
recently emerging immuno-checkpoint inhibitors such as nivolumab and pembrolizumab are also in early development and are commonly used in second-line treatments.
the lack of effective treatment and low survival rate of most liver cancer patients, the development of new liver cancer drugs has become an urgent need.
I statins improve hepatocellular carcinoma (HCC) Has been conducted in several preclinical and clinical studies showing that statin use is associated with reduced mortality from a variety of cancers, including hepatocellular carcinoma (HCC).
For viral-related hepatocellular carcinoma (HCC), a study involving 328,946 HBV-infected patients (incidence of hepatocellular carcinoma was 310.4/100,000) showed a negative correlation between the incidence of hepatocellular carcinoma (HCC) and the use of statins.
, a wide-ranging study of HCV infections showed that a decrease in the risk of hepatocellular carcinoma (HCC) was closely related to the use of statins.
these studies have shown that statin use can help improve HBV and HCV-related hepatocellular carcinoma (HCC).
2 statins improve the potential mechanisms of hepatocellular carcinoma (HCC) As shown in Figure II, Simvastatin exhibits dose-dependent inhibition on both human hepatoblastoma cells (Huh6) and HepG2 cells.
In addition to inhibiting tumor cell flux, statins have been found to improve the potential mechanisms of hepatocellular carcinoma (HCC), tumor cell apoptosis, angiogenesis, tumor cell invasion, inflammation, liver fibrosis, and HCV pathogenis.
Figure III statins affect cancer mechanisms specifically, as shown in Figure III, there are now indications that cerivastatin, lovastatin, and simvastatin inhibit tumor proliferation.
, cerivastatin blocks the proliferation of Ras and Rho-mediated cells; lovastatin inhibits the activation of protease pathways, which leads to p21 and p27 stabilization; and Lovastatin Lovastatin blocks G1/S and G2/M conversions, blocking cell cycles, and simvastatin and lovastatin combined to inhibit hepatocellular proliferation and collagen steady state levels.
, fluvastatin, simvastatin, and lovastatin, among the statins that induce apoptosis, can reduce MVA path and isoprene modifications that inhibit small G proteins; simvastatin activates the JNK path through downstream superoxidation mediating to make non-classical adjustments to RhoA and Rac1 GTPases; Simvastatin activates Bax and lowers BCL-2; lovastatin activates caspase; and inhibits BCL-2 and ups and down Bax (by adjusting MEK-ERK path; atovastatin activates caspase-9 and caspase-3 in liver astrology cells; fluvastatin In association with celecoxib, pAkt, myeloid leukemia 1 (Mcl1) and survivin protein were lowered with the upward cell cycle protein-dependent kinase inhibitor p21 (Waf1/Cip1).
addition, statins that affect angiogenesis and tumor cell invasion are: cerivastatin, atovastatin and simvastatin; The CV course is called lovastatin; simvastatin, which inhibits the proliferation of embryonic stem cells; and atorvastatin, which inhibits myc phosphorylation and activation.
, we can see that statins help improve liver cancer and have been proven by a large number of clinical and scientific trials.
, based on statins, new liver cancer drugs can be developed through new, joint and structural modification of old drugs.
can be confident that statins will continue to surprise us.
: The illustration of the article is from Reference 1 Reference: 1. Hepatocellular Carcinoma and Statins,2020;2. Systematic review with network meta-analysis: statins and risk of hepatocellular carcinoma,2016;3. The immunology of hepatocellular carcinoma,2018.