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Prof. Wang Jianliu's Team Firstly Proposes New Strategy for Treatment of Diabetes-related Endometrial Cancer

2022-04-18

Prof. Wang Jianliu’s team from the Department of Obstetrics and Gynecology at Peking University People’s Hospital has been focusing on the research of the occurrence, development and treatment of endometrial cancer for many years, and has presided over a number of scientific research projects at national and provincial levels. Recently, his team published research results in Advanced Science (IF: 16.806), with the title “Targeting Cancer Metabolism Plasticity with JX06 Nanoparticles via Inhibiting PDK1 Combined with Metformin for Endometrial Cancer Patients with Diabetes”. The research demonstrated that the combination of JX06-NPs and Met can target the cancer metabolism plasticity, which significantly inhibits the growth of EC, thereby provides a new adjuvant therapy for patientsEC+/dia+.

 

 

Diabetes is closely related to the occurrence of endometrial cancer (EC) and its poor prognosis. However, there is no effective clinical treatment for EC patients with diabetes (patientEC+/dia+). To explore new therapeutic targets, the researchers first established an EC cell line Ishikawa cultured at a long-term high glucose (IshikawaHG) concentration, with the same cell line cultured at a normal glucose (IshikawaNG) concentration as the control group. Subsequently, it is discovered that IshikawaHG exhibits glucose metabolic reprogramming characterized by increased glycolysis and decreased oxidative phosphorylation. Further, pyruvate dehydrogenase kinase 1 (PDK1) is identified to promote glycolysis of IshikawaHG by proteomics. Most importantly, JX06, a novel PDK1 inhibitor combined metformin (Met) significantly inhibits IshikawaHG proliferation though IshikawaHG is resistant to Met. Furthermore, a reduction-sensitive biodegradable polymer is adopted to encapsulate JX06 to form nanoparticles (JX06-NPs) for drug delivery. It is found that in vitro JX06-NPs have better inhibitory effect on the growth of IshikawaHG as well as patient-derived EC cells (PDC) than JX06. Additionally, it is found that JX06-NPs can accumulate to the tumor of EC-bearing mouse with diabetes (miceEC+/dia+) after intravenous injection, and JX06-NPs combined Met can significantly inhibit tumor growth of miceEC+/dia+. The above results together suggested that the combination of JX06-NPs and Met has shown an enhanced antitumor effect under a high-glucose condition, providing a new strategy for the treatment of patientsEC+/dia+.

 

Dr. Yang Xiao, Dr. Cheng Yuan and Dr. Zhou Jingyi are the co-first authors of the article. Prof. Wang Jianliu and Prof. XiaoHaihua are the co-corresponding authors. The study was supported by the National Key Technology R & D Program of China, the National Natural Science Foundation of China and the Natural Science Foundation of Beijing.

 

Paper Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922133/