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Effects of immunisation against PCSK9 in mice bearing melanoma.
Archives of Medical Science ( IF 3.8 ) Pub Date : 2019-12-31 , DOI: 10.5114/aoms.2020.91291
Amir Abbas Momtazi-Borojeni 1, 2 , Maryam Ebrahimi Nik 3 , Mahmoud Reza Jaafari 4, 5 , Maciej Banach 6, 7 , Amirhossein Sahebkar 5, 8, 9
Affiliation  

INTRODUCTION Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an established modality for the treatment of hypercholesterolaemia. However, the impact of PCSK9 inhibition in other situations such as cancer remains largely unknown. The current study was conducted to study the effects of PCSK9 inhibition on cancer endpoints in mice bearing melanoma. MATERIAL AND METHODS To generate antiPCSK9 antibody in vivo, a nanoliposomal antiPCSK9 vaccine adsorbed to 0.4% Alum adjuvant was subcutaneously injected in C57BL/6 mice four times with bi-weekly intervals. Two weeks after the last immunisation, mice were subcutaneously inoculated with B16F0 melanoma cells. After a tumour mass was palpable (approximately 10 mm3), the mice were randomly divided into four groups and subjected to different treatment protocols: (1) PBS (untreated control), (2) vaccine group, (3) the combination of vaccine and a single dose of liposomal doxorubicin (Doxil®), and (4) liposomal doxorubicin (positive control) group. To determine therapeutic efficacy, mouse body weight, tumour size, and survival were monitored every three days for 36 days. RESULTS The nanoliposomal antiPCSK9 vaccine was found to efficiently induce specific antibodies against PCSK9 in C57BL/6 mice, thereby reducing plasma levels and function of PCSK9. Tumour volumes in the vaccinated group were not significantly different from those in the liposomal doxorubicin, combination, and control groups. The time to reach endpoint (TTE) values of the vaccine (28 ±5 days), combination (30 ±6 days), liposomal doxorubicin (34 ±2 days), and control (31 ±2 days) groups were not significantly different, either. Furthermore, the tumour growth delay (TGD) values of the vaccine (-11.5 ±15.4%), liposomal doxorubicin (7.75 ±6.5%), combination (-6 ±20.77%), and control (0 ±7.5) groups were not significantly different. Finally, there was no significant difference between the median survival time and lifespan of the vaccinated versus other tested groups. CONCLUSIONS The nanoliposomal PCSK9 vaccine did not adversely affect the growth of melanoma tumour nor the survival of tumour-bearing mice.

中文翻译:

对携带黑色素瘤的小鼠的 PCSK9 免疫效果。

引言 抑制前蛋白转化酶枯草杆菌蛋白酶/kexin 9 (PCSK9) 是治疗高胆固醇血症的既定方式。然而,PCSK9 抑制在癌症等其他情况下的影响仍然很大程度上未知。目前的研究旨在研究 PCSK9 抑制对黑色素瘤小鼠癌症终点的影响。材料和方法为了在体内产生抗PCSK9抗体,将吸附在0.4%明矾佐剂上的纳米脂质体抗PCSK9疫苗以两周一次的间隔在C57BL/6小鼠中皮下注射四次。最后一次免疫后两周,给小鼠皮下接种 B16F0 黑色素瘤细胞。在可触及肿瘤块(约 10 mm3)后,将小鼠随机分为四组并接受不同的治疗方案:(1)PBS(未治疗的对照),(2)疫苗组,(3)疫苗与单剂量脂质体多柔比星(Doxil®)联合用药,(4)脂质体多柔比星(阳性对照)组。为了确定治疗效果,每三天监测一次小鼠体重、肿瘤大小和存活率,持续 36 天。结果发现纳米脂质体抗PCSK9疫苗可在C57BL/6小鼠体内有效诱导针对PCSK9的特异性抗体,从而降低血浆水平和PCSK9的功能。接种组的肿瘤体积与脂质体多柔比星组、联合组和对照组的肿瘤体积没有显着差异。疫苗组(28 ±5 天)、联合组(30 ±6 天)、脂质体阿霉素(34 ±2 天)和对照组(31 ±2 天)的达到终点 (TTE) 值的时间没有显着差异,任何一个。此外,疫苗(-11.5±15.4%)、脂质体阿霉素(7.75±6.5%)、联合(-6±20.77%)和对照组(0±7.5)组的肿瘤生长延迟(TGD)值没有显着差异。最后,接种疫苗的组与其他测试组的中位生存时间和寿命之间没有显着差异。结论 纳米脂质体 PCSK9 疫苗不会对黑色素瘤的生长和荷瘤小鼠的存活产生不利影响。
更新日期:2019-12-31
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