AUTHOR=Wang Jiahui , Song Yijie , Zhang Ning , Li Ning , Liu Congying , Wang Bing 

TITLE=Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.658543

DOI=10.3389/fonc.2021.658543

ISSN=2234-943X

ABSTRACT=<sec><title>Aim of the Study</title><p>CHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having <italic>in vivo</italic> toxicity, CHE has not been thoroughly investigated in term of its <italic>in vivo</italic> antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827.</p></sec><sec><title>Methods</title><p>The antitumor effect of CHE on HCC827 was evaluated, and its potential work mechanism was investigated. CHE long circulation liposomes (CHELPs) modified with polyethylene glycol have been optimized and characterized by <italic>in vivo</italic> pharmacokinetic studies. A HCC827 xenograft model was developed on BALB/c nude mice for the assessment of the effects of CHE and CHELP.</p></sec><sec><title>Results</title><p>CHE might inhibit HCC827 growth through the ROS/PKC-<italic>ϵ</italic>/caspase 3 pathway and glycolysis. The optimized CHELP remained stable after storage for 10 days at 4°C and exhibited sustained drug release, showing approximately one-fifteenth of the <italic>in vivo</italic> clearance rate and 86 times the absorption concentration of free drug. While increasing the bioavailability of CHE, CHELP showed a good therapeutic effect on HCC827 tumor-bearing nude mice and reduced the toxicity of the free drug, improving the safety of CHE.</p></sec><sec><title>Conclusions</title><p>CHE is a candidate drug for NSCLC, and liposomes are effective in alleviating the toxicity of CHE.</p></sec>