A schema of the potential mechanisms underlying SeS2-induced proliferation inhibition and apoptosis of HCC cells

As the most common form of liver cancer with high incidence rate and susceptibility to metastasis and recurrence, hepatocellular carcinoma (HCC) has posed a major threat to human health.

It is of great urgency to identify optional therapeutic targets and develop novel effective drugs since conventional therapeutic treatments have such problems as major side effects, drug overuse and drug resistance. Research shows that pleomorphic adenoma gene like-2 (PLAGL2) is closely associated with the invasion and metastasis of malignant tumors, drug resistance and adverse effects. 

As a transcription factor, PLAGL2 can regulate multiple genes related to cell proliferation, angiogenesis and the metastasis of malignant tumors. It is believed to be a major promising therapeutic target in the treatment of malignant tumors. Therefore, there is value in conducting further studies in the regulatory mechanism and targeting inhibition effects of PLAGL2 for therapeutic treatment of malignant tumors.

During a recent study, Zhang Yanmin, a professor with the School of Pharmacy of the Health Science Center of Xi'an Jiaotong University (XJTU), and his research team observed overexpression of PLAGL2 in tumor issues of patients with liver cancer and confirmed that the overexpression can promote the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C-MET/STAT3 signaling axis.

In addition, their research revealed that selenium sulfide (SeS2) can dramatically inhibit the proliferation of cancer cells and induce mitochondrial apoptosis in HCC cells through PLAGL2-dependence. Its functional mechanism is to suppress C-MET/STAT3, AKT/mTOR, and MAPK signaling and trigger Bcl-2/Cyto C/Caspase-mediated cascades both in vitro and in vivo.

The research has provided theoretical support for the development of PLAGL2-targeted drug candidates for HCC therapy and laid an experimental foundation for future studies of SeS2.

The research was recently published in the journal Clinical and Translational Medicine. Yang Tianfeng, a Ph.D. student with the School of Pharmacy of the Health Science Center at XJTU, was the first author of the paper. Its corresponding authors were Professor Zhang and Associate Professor Dai Bingling.

The research received support from the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities and the XJTU Program for Training Young Talents.

Profiles of Yang Tianfeng and Zhang Yanmin

Yang has published 29 SCI (Science Citation Index) papers and acted as the first author or co-first author of 11 SCI papers published in scientific journals such as ClinTransl Med, Cancer Lett, Biomaterials, Appl Mater Today, Int J Nanomed and Biomed Pharmacother.

Zhang, Yang’s academic supervisor, has engaged in the development and analytical research of drug candidates for malignant tumors therapy for decades. He is the director of the Shaanxi Natural Medicines Research and Engineering Key Laboratory, the head of the XJTU Institute of Vascular Medicines, and a member of the board of editors of such SCI journals as Biosensors, Oncol Rep and Mol Med Rep. 

He has published 136 SCI papers, received 20 national patents of invention, and won the second prize of the State Award for Technological Invention, the second prize of the Shaanxi Provincial Science and Technology Award and the second prize of the Chinese Pharmaceutical Association Science and Technology Award. 

Zhang has been listed as a national excellent talent in the new century, a young leading talent in scientific and technological innovation in Shaanxi, a young star in science and technology in Shaanxi and an A-level young talent at XJTU.