Misir Krpan Ana, Ivankovic Sinisa, Krajina Zdenko, Ivankovic Dusica, Stojkovic Ranko
Center of Oncology and Radiotherapy, Clinic of Oncology and Radiotherapy, University Hospital Center Zagreb, Zagreb, Croatia.
Tumori. 2012 Mar-Apr;98(2):257-63. doi: 10.1177/030089161209800213.
The aim of the study was to investigate whether use of the antiestrogen tamoxifen and heat treatment in combined therapy with the well-known anticancer drugs cisplatin, dacarbazine and cyclophosphamide enhances their therapeutic efficacy on mouse B16-F10 melanoma in vivo. The results of systemic melanoma therapy have been mostly disappointing. Therefore, there is still a great need for strategies that can improve existing chemotherapy options.
The tumor model for the investigation of antitumor activity was a mouse B16-F10 melanoma transplanted into the footpad of C57BL/6 Zgr/Hr mice. Drugs were given intraperitoneally 15 min before the application of local hyperthermia, and tumor growth and mouse survival were followed.
Hyperthermia alone determined a significant delay of tumor growth, but mouse survival was not affected. In bimodal combinations with hyperthermia, all the tested antitumor drugs significantly increased both tumor growth delay and mouse survival. Tamoxifen alone did not show any inhibitory effect on B16-F10 melanoma in vivo. However, in the trimodal therapy with a particular drug and hyperthermia, it potentiated the inhibitory effects of the respective bimodal treatments, especially that of cyclophosphamide and hyperthermia.
Our results obtained on the mouse B16-F10 melanoma in vivo confirmed the enhanced therapeutic efficacy of the trimodal therapy tamoxifen, hyperthermia and anticancer drug combinations in melanoma treatment. Further studies should optimize the heat-drug time scheduling and drug doses that will result in the best possible therapeutic achievement for these trimodal therapy options.
本研究旨在探讨抗雌激素他莫昔芬以及热疗与知名抗癌药物顺铂、达卡巴嗪和环磷酰胺联合使用时，是否能增强它们对小鼠B16-F10黑色素瘤的体内治疗效果。全身性黑色素瘤治疗的结果大多令人失望。因此，仍迫切需要能够改善现有化疗方案的策略。
用于研究抗肿瘤活性的肿瘤模型是将小鼠B16-F10黑色素瘤移植到C57BL/6 Zgr/Hr小鼠的足垫中。在进行局部热疗前15分钟腹腔注射药物，然后观察肿瘤生长情况和小鼠存活情况。
单独热疗可显著延迟肿瘤生长，但不影响小鼠存活。在与热疗的双峰联合治疗中，所有测试的抗肿瘤药物均显著增加了肿瘤生长延迟时间和小鼠存活时间。他莫昔芬单独使用时对体内B16-F10黑色素瘤未显示出任何抑制作用。然而，在特定药物与热疗的三峰联合治疗中，它增强了各自双峰治疗的抑制作用，尤其是环磷酰胺与热疗联合的效果。
我们在小鼠B16-F10黑色素瘤体内获得的结果证实了他莫昔芬、热疗和抗癌药物联合的三峰联合治疗在黑色素瘤治疗中具有增强的治疗效果。进一步的研究应优化热疗与药物的时间安排以及药物剂量，以使这些三峰联合治疗方案取得最佳治疗效果。
