Cisplatin-Induced Giant Cells Formation Is Involved in Chemoresistance of Melanoma Cells

International Journal of Molecular Sciences

Jian-Ching Wu¹  Chien-Hui Weng²  Ming-Hong Tai²  Chieh-Shan Wu³  Mei-Lang Kung⁴  Ming-Hsiu Wu⁵ 

[1] Biobank and Tissue Bank, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan;Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan;Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan;Department of Nutrition and Health Science, Fooyin University, Kaohsiung 83102, Taiwan;

关键词: melanoma;    chemoresistance;    cisplatin;    giant cell;    stemness;   

DOI  :  10.3390/ijms21217892

来源: DOAJ

【 摘 要 】

Melanoma is notoriously resistant to current cancer therapy. However, the chemoresistance mechanism of melanoma remains unclear. The present study unveiled that chemotherapy drug cisplatin induced the formation of giant cells, which exhibited enlargement in cell diameter and nucleus in mice and human melanoma cells. Giant cells were positive with melanoma maker S100 and cancer stem cell markers including ABCB5 and CD133 in vitro and in vivo. Moreover, giant cells retained the mitotic ability with expression of proliferation marker Ki-67 and exhibited multiple drug resistance to doxorubicin and actinomycin D. The mitochondria genesis/activities and cellular ATP level were significantly elevated in giant cells, implicating the demand for energy supply. Application of metabolic blockers such as sodium azide or 2-deoxy glucose abolished the cisplatin-induced giant cells formation and expression of cancer stemness markers. The present study unveils a novel chemoresistance mechanism of melanoma cells via size alteration and the anti-neoplastic strategy by targeting giant cells.

【 授权许可】

Unknown