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Publications

Journal Article Epublish

PubMed: 40561066 DOI: 10.1371/journal.pone.0327144

HMGB1-BoxA gene therapy in reversing cisplatin resistance in non-small cell lung cancer.

PLoS One 20(6):e0327144

Authors: Nattapong Puthdee, Van-Hieu Mai, Sirapat Settayanon, Pithi Chanvorachote, Chatchawit Aporntewan, Apiwat Mutirangura, Chanida Vinayanuwattikun

Affiliations

  • C2F-Postdoctoral Fellowship, Chulalongkorn University, Bangkok, Thailand.
  • Faculty of Medicine, University of Health Sciences, Vietnam National University Ho Chi Minh City, Vietnam.
  • Graduate Program in Clinical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand. Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Cell-Based Drug and Health Product Development Research Unit and Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
  • Department of Mathematics and Computer Sciences & Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  • Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Abstract

Cisplatin is a widely used chemotherapy agent in the treatment of non-small cell lung cancer (NSCLC). However, its clinical efficacy is limited by the development of drug resistance in patients with NSCLC. Recently, we demonstrated that HMGB1-BoxA gene therapy (BoxA) is an ideal cancer treatment that revitalizes normal cells while promoting cancer cells' DNA break cascade. Increasing cytoplasmic HMGB1 is a reason for cisplatin resistance (Cis-R); in this study, we investigated the potential of BoxA to reverse acquired cisplatin resistance in two NSCLC cell lines, A549/Cis-R, and H460/Cis-R. The growth capacity of these cancer cells was significantly impaired upon BoxA treatment, resulting in a notable reduction in cell viability, colony formation, cancer stemness, and self-renewal capacity. Significantly, BoxA enhanced cisplatin sensitivity and promoted apoptosis in cisplatin-treated Cis-R cells. Furthermore, BoxA altered the subcellular localization of the HMGB1 protein, decreasing its cytoplasmic localization. BoxA can potentially reverse cisplatin resistance by altering the translocation of HMGB1.

MeSH

Cells, Genes, Lung, Neoplasms, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Small Cell Lung Carcinoma, Therapeutics, Hmgb1 Protein