为探讨磁流体靶向热疗对小鼠胰腺癌的体外和动物治疗作用,利用前期建株的小鼠胰腺腺泡细胞癌株(MPC-83)分别进行体外热疗和动物实验.对MPC-83 进行水浴热疗,分别调热疗温度为37、42、46、50℃,作用30 min,显微镜观察细胞形态变化,流式细胞仪检测凋亡和坏死细胞百分比.选择4 周龄雌性昆明种小鼠,建立MPC-83 胰腺癌皮下肿瘤模型,观察磁流体热疗(46℃和50℃)对荷瘤小鼠的作用及其病理学变化.流式细胞仪检测46℃和50℃热疗细胞凋亡和坏死百分比分别为46.13%、89.33%,与对照组比较,差异具有统计学意义(P<0.05).热疗后第14 天,46℃和50℃热疗组肿瘤生长率分别为-0.64±0.73和-0.72±0.79,与3 个对照组比较,肿瘤生长受到明显抑制(P<0.05).病理学检查示磁流体对照组,在注射磁流体24 h 可见散在的磁性纳米微粒在一定范围内分布于肿瘤细胞之间,部分肿瘤细胞和吞噬细胞吞噬了磁性纳米微粒.热疗14 d 肿瘤完全消失的小鼠皮下组织未见肿瘤细胞,可见皮下残存磁性纳米微粒,被吞噬细胞吞噬.各对照组小鼠瘤体生长旺盛,细胞核浓染分裂,可见病理性核分裂像.磁流体靶向热疗可以达到杀伤胰腺癌细胞的理想温度,能有效抑制MPC-83 胰腺癌生长,延长小鼠生存期.
This paper aims to assess the therapeutic effect of magnetic fluid hyperthermia (MFH) on mouse pancreatic cancer in vitro and in vivo. In vitro and in vivo experiments were respectively established using the unique mouse pancreatic cancer cell line (MPC- 83). Apoptosis and morphological changes of the MPC-83 were measured with flow cytometry and microscopy after heating to 42, 46, and 50℃ with water bath for 30 min. Four-week-old female Kunming mice were selected to establish subcutaneous pancreatic cancer model. The therapeutic effect (46℃ and 50℃) was evaluated by detecting various influences including pathological examination. Flow cytometry revealed the apoptosis and necrosis rate of MPC-83 were 46.13% (46℃) and 89.33% (50℃). Fourteen days after hyperthermia, the tumor growth rate were -0.64±0.73 and -0.72±0.79, which were significantly lower than that in each control group (P<0.05). Compared with control groups, tumor growth in the experimental group was markedly inhibited. Pathological examination showed that magnetic nanoparticles were distributed between tumor cells, and some of them were ingested by phagocytes. Fourteen days after hyperthermia, there were no subcutaneous nodules with only the MF remaining. In each control group, tumor cells grew very well, and hyperchromatic nuclei and pathological karyokinesis were seen simultaneously. MFH can reach perfect therapeutic temperature and heat tumor tissue specifically, inhibiting the growth of mouse pancreatic cancer and prolonging the survival time of the mice apparently. MFH has satisfactory therapeutic efficacy for mouse pancreatic cancer.
[1] Long J, Luo G P, Xiao Z W, et al. Cancer statistics: Current diagnosis and treatment of pancreatic cancer in Shanghai, China[J]. Cancer Letters, 2014, pii: S0304-3835(14)00030-5.
[2] Wang L, Dong J, Ouyang W, et al. Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles[J]. Oncology Reports, 2012, 27(3): 719-726.
[3] Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010[J]. CA: A Cancer Journal for Clinicians, 2010, 60(5): 277-300.
[4] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA: A Cancer Journal for Clinicians, 2012, 62(1): 10-29.
[5] Parchur A K, Ansari A A, Singh B P, et al. Enhanced luminescence of CaMoO4: Eu by core@shell formation and its hyperthermia study after hybrid formation with Fe3O4: Cytotoxicity assessment on human liver cancer cells and mesenchymal stem cells[J]. Integrative Biology (Cambridge), 2014, 6(1): 53-64.
[6] Taratula O, Dani R K, Schumann C, et al. Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells[J]. International Journal of Pharmaceutics, 2013, 458(1): 169-180.
[7] Oliveira T R, Stauffer P R, Lee C T, et al. Magnetic fluid hyperthermia for bladder cancer: A preclinical dosimetry study[J]. International Journal of Hyperthermia, 2013, 29(8): 835-844.
[8] Portela A, Vasconcelos M, Fernandes M H, et al. Highly focalised thermotherapy using a ferrimagnetic cement in the treatment of a melanoma mouse model by low temperature hyperthermia[J]. International Journal of Hyperthermia, 2013, 29(2): 121-132.
[9] Kobayashi D, Kawai N, Sato S, et al. Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model[J]. Prostate, 2013, 73(9): 913-922.
[10] Jordan A. First clinical experience with magnetic field hyperthermia (MFH) at the university clinic charite in Berlin[C]. 5th International Conference on the Scientific and Clinical Application for Mangetic Carriers, 2004, May 20-22, Lyon, France.
[11] Maier-Hauff K, Ulrich F, Nestler D, et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron- oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme[J]. Journal of Neurooncology, 2011, 103(2): 317-324.
[12] Johannsen M, Thiesen B, Wust P, et al. Magnetic nanoparticle hyperthermia for prostate cancer[J]. International Journal of Hyperthermia, 2010, 26(8): 790-795.
[13] van Landeghem F K, Maier-Hauff K, Jordan A, et al. Post-mortem studies in glioblastoma patients treated with thermotherapy using magnetic nanoparticles[J]. Biomaterials, 2009, 30(1): 52-57.
[14] Ouyang W, Gao F, Wang L, et al. Thermoseed hyperthermia treatment of mammary orthotopic transplantation tumors in rats and impact on immune function[J]. Oncology Reports, 2010, 24(4): 973-979.
