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Assessment of a Polyfl-uorinated and Platinum-Based Analogue against Triple-Negative Breast Cancer 1) Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Abstract Breast cancer is the most common cause of deaths in women suffered from cancers in the 20th century. Especially in patients with triple-negative breast cancer (TNBC), they displayed higher recurrence rate and more aggressive stage after diagnosis. DNA-damaging agents, such as cisplatin, served as a successful approach against breast cancer. However, drug resistance has been reported in clinical practice after a long-term course of treatments. To investigate a new medicine with the improved therapeutic efficacy and declined side effects, we performed a new platinum-based compound with polyfluorinated modification and bipyridine structure in this study. The anti-cancer effects of the potential candidate, dichloro [4,4^-bis(2,2,3,3-tetrafluoropropoxy) methyl)-2,2^-bipryridine] platinum (TFBPC), were majorly determined in MDA-MB-231 human breast cancer cells and xenograft models. Results demonstrated that TFBPC targeting to calf-thymus DNA and circular plasmids resulted in the formation of DNA crosslinks, DNA degradation and cell death program through PARP/Bax/Bcl-2 apoptosis and LC3-related autophagy pathway. In cell line-derived xenograft models, TFBPC significantly inhibited tumor growth without the induction of pathological changes in hematological and biochemistry tests. TFBPC also decreased the expressions of P53, Ki-67 and PD-L1 and increased cleaved caspase 3 expressions in tumors. These results revealed a new achievement to overcome cisplatin resistance and to be a potential strategy in patients with triple-negative breast cancer. For further investigations, details in drug-DNA interaction and pharmacokinetics could be conducted. Keywords: cisplatin- xenograft model- triple-negative breast cancers- apoptosis- autophagy Topic: Biology |
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