Department of Anesthesiology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, No. 252 East Street, Quanzhou, 362000, Fujian, China.
Department of Orthopaedics, The First Hospital of Quanzhou Affiliated to Fujian Medical University, No. 252 East Street, Quanzhou, 362000, Fujian, China.
Inflammopharmacology. 2018 Apr;26(2):395-402. doi: 10.1007/s10787-017-0388-2. Epub 2017 Aug 20.
Bone pain associated with advanced tumor metastasis is the most severe threat to life quality of patients. Highly efficient and low-toxic therapeutics is of urgent need for this complication. Bone tumor metastasis was established by direct bone inoculation of Walker 256 mammary gland carcinoma cells. Bone nociception was measured by mechanical allodynia, thermal hyperalgesia and spontaneous flinches. P2X7R level was determined by immunoblotting. The inward current was recorded by a patch clamp. The related cytokines were determined by ELISA. Our results showed that teniposide (TN) treatment significantly ameliorated bone nociception associated with tumor inoculation to a comparable extent with P2X7-specific inhibitor, BBG, in rat model. The efficient blockade of inward current generation and pro-inflammatory cytokines secretion were observed upon administration with TN. Our data highlighted the therapeutic potency of TN in this complication associated with tumor metastasis and warrants further clinical investigations.
骨转移相关的骨痛是晚期肿瘤患者生命质量受到的最严重威胁。对于这种并发症,急需高效低毒的治疗方法。通过直接向骨内接种 Walker 256 乳腺癌细胞来建立骨肿瘤转移模型。通过机械性痛觉过敏、热痛觉过敏和自发性抽搐来测量骨痛觉。通过免疫印迹法测定 P2X7R 水平。用膜片钳记录内向电流。通过 ELISA 测定相关细胞因子。我们的研究结果表明,依托泊苷(TN)治疗可显著改善与肿瘤接种相关的骨痛觉,其疗效与 P2X7 特异性抑制剂 BBG 相当。TN 给药后可有效阻断内向电流的产生和促炎细胞因子的分泌。我们的数据突出了 TN 在这种与肿瘤转移相关的并发症中的治疗潜力,值得进一步的临床研究。