Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model
Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model
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DOI：
10.1002/pros.22637
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发表时间：
2013-06-01
期刊：
影响因子：
2.8
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Kobayashi, Daichi;Kawai, Noriyasu;Kohri, Kenjiro
背景骨转移是前列腺癌患者面临的严重问题，抗癌药物多西他赛（DTX）的疗效不足。因此，我们研究了磁性阳离子脂质体（MCL）在一种新的大鼠模型中的治疗潜力，该模型可以评估肿瘤免疫力。比较MCL热疗与传统DTX治疗前列腺癌骨转移的疗效。方法将前列腺肿瘤组织移植于模型大鼠股骨内，分为对照组、MCL组、DTX组和MCL+DTX组。肿瘤注射MCL，并进行交变磁场（AMF）照射，每周三次。通过增殖细胞核抗原阳性、计算机断层扫描和CD68阳性细胞数评价肿瘤增殖和骨破坏，通过热休克蛋白（HSP）70表达和CD8阳性淋巴细胞数评价肿瘤免疫。结果成功建立了一种新型的前列腺癌股骨转移模型，与对照组和DTX组相比，MCL组和MCL+DTX组的肿瘤增殖和骨破坏明显受到抑制。MCL热疗同时诱导细胞坏死和凋亡。MCL组和MCL+DTX组HSP70的表达也明显增加，并通过诱导CD8阳性淋巴细胞而增强肿瘤免疫。结论MCL热疗治疗前列腺癌骨转移的疗效明显优于DTX。因此，MCL热疗和DTX的组合值得考虑作为这种疾病的新治疗方法。前列腺73：913922，2013年。(c)2013 Wiley Periodicals，Inc.
BACKGROUND Bone metastasis is a serious problem for individuals with prostate cancer, and the effects of the anticancer drug docetaxel (DTX) are insufficient. We therefore examined the therapeutic potential of magnetic cationic liposomes (MCL) in a novel rat model that allows the evaluation of tumor immunity. The effects of MCL thermotherapy were compared with those of DTX as a conventional therapy for the treatment of bone metastatic prostate cancer. METHODS Prostate tumor tissues were transplanted into the femurs of model rats divided into four groups: control, MCL, DTX, and MCL+DTX. Tumors were injected with MCL, and alternating magnetic field (AMF) irradiation was performed three times a week. Tumor proliferation and bone destruction were evaluated by proliferating cell nuclear antigen positivity, computed tomography, and CD68-positive cell number, while tumor immunity was evaluated by heat shock protein (HSP) 70 expression and CD8-positive lymphocyte number. RESULTS We successfully established a novel femur metastasis model of prostate cancer, and demonstrated that tumor proliferation and bone destruction in the MCL and MCL+DTX groups were significantly suppressed compared with control and DTX groups. MCL thermotherapy concurrently induced necrosis and apoptosis. The expression of HSP70 in the MCL and MCL+DTX groups was also significantly increased, and tumor immunity was enhanced through the induction of CD8-positive lymphocytes. CONCLUSION MCL thermotherapy was clearly more effective than DTX in treating bone metastatic prostate cancer. A combination of MCL thermotherapy and DTX therefore deserves consideration as a novel treatment for this disease. Prostate 73: 913922, 2013. (c) 2013 Wiley Periodicals, Inc.