关键词: DDP P2X7 human osteosarcoma shock wave

来  源:   DOI:10.1097/MS9.0000000000001909   PDF(Pubmed)

Abstract:
UNASSIGNED: The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects.
UNASSIGNED: To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors\' results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7.
UNASSIGNED: For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.
摘要:
目前骨肉瘤治疗的困境是长期使用后化疗药物的耐药性,这也带来了危及生命的副作用。
为了减少骨肉瘤患者的化疗耐药性,作者将冲击波(SWs)应用于人类骨肉瘤MNNG/HOS细胞,然后评估细胞活力和细胞外ATP水平,并进一步研究了SWs对MNNG/HOS细胞顺铂(DDP)细胞毒性的影响。作者的结果表明,在0.21mJ/mm2的400个SW脉冲对MNNG/HOS细胞活力的影响很小。此外,这种SW条件显着促进了MNNG/HOS细胞的细胞外ATP释放。重要的是,低能量SWs明显增加MNNG/HOS细胞中Akt和哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化和活化,在P2X7siRNA存在下可以部分逆转。作者还发现,在不存在P2X7的情况下,低能量SWs强烈增加了MNNG/HOS细胞的DDP敏感性。
第一次,作者发现,当ATP受体P2X7下调时,SW治疗可降低MNNG/HOS骨肉瘤细胞的DDP抵抗.SW疗法可能为化学抗性人骨肉瘤提供新的治疗策略。
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