Nowarta110治疗HPV-16和HPV-18肿瘤基因转化人体细胞和癌症植入动物模型的疗效研究。

IF 1.6 4区 医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17298
Jon Sin, Matei Kiosea, Khosrow Mahdavi, Ferre Akbarpour, Jolie Nguyen, B O Han, Ba X Hoang
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引用次数: 0

摘要

背景/目的:宫颈癌是全球妇女因癌症死亡的第三大原因。几乎所有的宫颈癌病例都是由于感染了人类乳头瘤病毒(HPV)所致。诺伐他110在针对跖疣的II期临床研究中显示出突破性疗效,且无任何副作用报道。本研究采用阴道移植和皮下注射两种动物癌症模型,评估了 Nowarta110 杀死培养的人乳头瘤病毒转化癌细胞的有效性及其对小鼠的抗癌作用:Nowata110 是一种新型化合物,由胶体银和无花果提取物组成。对 Nowarta110 在 HPV-16 和 HPV-18 转化的人类癌细胞(分别为 ARPE-19/HPV-16 和 HeLa 细胞)上的细胞毒性特性进行了评估。在 ME-180 表皮样癌细胞移植到小鼠阴道或皮下后,对 Nowarta110 的体内治疗潜力进行了评估。当肿瘤体积达到约 65 立方毫米时,开始使用 Nowarta110 治疗:我们的数据显示,表达 HPV16 的人视网膜色素上皮细胞易受 Nowarta110 诱导的细胞死亡影响,1% 的 Nowarta110 会降低细胞存活率,5% 的 Nowarta110 则完全没有存活细胞。在表达 HPV18 的 HeLa 细胞中,Nowarta110 的剂量为 5%时会导致细胞迅速大量死亡,而较低的 1%剂量则不会产生同样的效果。动物实验结果表明,在阴道内和皮下肿瘤模型中,Nowarta110 都能有效诱导肿瘤消退:结论:Nowarta110 能有效诱导 HPV-16 和 HPV-18 转化的人类癌细胞死亡。结论:Nowarta110 能有效诱导 HPV-16 和 HPV-18 转化的人类癌细胞的细胞死亡,还能有效诱导阴道内接种或皮下植入癌细胞的小鼠模型的肿瘤消退。考虑到 HPV 引起的宫颈发育不良和癌症发病率高且缺乏治疗方法,有必要开展临床研究以推广 Nowarta110 的应用。
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Investigation of the Efficacy of Nowarta110 in the Treatment of HPV-16 and HPV-18 Oncogenically-transformed Human Cells and Cancer-implanted Animal Models.

Background/aim: Cervical cancer is the third leading cause of cancer-related death in women worldwide. Nearly all cases of cervical cancer are due to infection with human papillomavirus (HPV). Nowata110 has shown breakthrough therapeutic efficacy in phase II clinical study against plantar warts, with no reported side effects. This study evaluated the effectiveness of Nowarta110 in killing cultured HPV-transformed cancer cells and its anti-cancer effects in mice, using both vaginally engrafted and subcutaneously implanted animal cancer models.

Materials and methods: Nowata110 is a novel compound composed of colloidal silver and fig extract. The cytotoxic properties of Nowarta110 were evaluated on HPV-16 and HPV-18-transformed human cancer cells (ARPE-19/HPV-16 and HeLa cells, respectively). The therapeutic potential of Nowarta110 in vivo was evaluated following the engraftment of ME-180 epidermoid carcinoma cells in the mouse vagina or their subcutaneous implantation. Nowarta110 treatment was initiated when the tumor reached an approximate volume of 65 mm3 Results: Our data showed that HPV16-expressing human retinal pigmented epithelial cells are susceptible to Nowarta110-induced cell death, with a reduction in cell viability observed at 1% Nowarta110 and a complete absence of viable cells at 5% Nowarta110. In HPV18-expressing HeLa cells, Nowarta110 caused significant and rapid cell death at a dose of 5%, whereas lower doses of 1% did not produce the same effects. The results from animal studies indicated that Nowarta110 effectively induced tumor regression in both the intravaginal and subcutaneous tumor models.

Conclusion: Nowarta110 effectively induced cell death in HPV-16 and HPV-18-transformed human cancer cells. It also effectively induced tumor regression in mouse models with intravaginally engrafted or subcutaneously implanted cancer cells. Considering the high prevalence of HPV-induced cervical dysplasia and cancer and the lack of treatment, clinical studies to promote the implementation of Nowarta110 are warranted.

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来源期刊
Anticancer research
Anticancer research 医学-肿瘤学
CiteScore
3.70
自引率
10.00%
发文量
566
审稿时长
2 months
期刊介绍: ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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