Combination with a Low Dose of Doxorubicin Further Boosts the Antitumor Effect of SLURP-1 In Vivo and Associates with EGFR Down-Regulation.

IF 2 4区 生物学 Q4 CELL BIOLOGY
O V Shlepova, M L Bychkov, V O Shipunova, E I Shramova, M A Shulepko, T Y Gornostaeva, E A Kiseleva, I D Kukushkin, V A Kazakov, E A Tukhovskaya, I A Dyachenko, A N Murashev, Z O Shenkarev, S M Deyev, M P Kirpichnikov, E N Lyukmanova
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引用次数: 0

Abstract

Skin cancers such as squamous cell carcinoma (SCC) are among the most aggressive types of tumors. They come with a high rate of growth, metastasis, and frequently occurring chemoresistance. Smoking is one of the risk factors for SCC progression, and the α7 nicotinic acetylcholine receptor (α7-nAChR) is a promising target for SCC therapy. Human secreted protein SLURP-1 is an auto/paracrine regulator of epithelial homeostasis and a selective negative allosteric modulator of α7-nAChR. Recently, we demonstrated the high efficiency of the therapy based on the recombinant SLURP-1 in controlling SCC cell growth and metastasis in vivo. The anti-tumor effect of SLURP-1 was mediated through interaction with both α7-nAChR and the epidermal growth factor receptor (EGFR). Cytotoxic antibiotic doxorubicin has been proposed for the SCC therapy; however, its use is limited due to the high toxicity. In this study we investigated the use of an enhanced SLURP-1 dose and of a combination of SLURP-1 with low-dozen doxorubicin for SCC treatment of mice xenografted with squamous cell carcinoma A431 cells. An increased SLURP-1 dose didn't significantly enhance the efficiency of the therapy. However, the combination with doxorubicin further enhanced the anti- tumor activity of SLURP-1 and dramatically suppressed metastasis. The effect from the combined therapy was accompanied by down-regulation of EGFR expression in tumors. Direct inhibition of EGFR activation by SLURP-1 was shown. No toxicity of the combined therapy was encountered. Our data indicate that the combination of SLURP-1 with chemotherapy in lower doses is a promising approach in SCC treatment and should be further studied.

低剂量阿霉素联用进一步增强SLURP-1体内抗肿瘤作用并与EGFR下调相关。
皮肤癌如鳞状细胞癌(SCC)是最具侵袭性的肿瘤类型之一。它们具有较高的生长、转移率和经常发生的化疗耐药性。吸烟是SCC进展的危险因素之一,α7烟碱乙酰胆碱受体(α7- nachr)是SCC治疗的一个有希望的靶点。人分泌蛋白SLURP-1是上皮稳态的自分泌/旁分泌调节剂和α7-nAChR的选择性负变构调节剂。最近,我们证明了基于重组SLURP-1的治疗在体内控制SCC细胞生长和转移方面的高效率。SLURP-1的抗肿瘤作用是通过与α7-nAChR和表皮生长因子受体(EGFR)相互作用介导的。细胞毒性抗生素阿霉素已被建议用于SCC治疗;然而,由于其高毒性,其使用受到限制。在这项研究中,我们研究了使用提高SLURP-1剂量和SLURP-1与低剂量阿霉素联合治疗鳞状细胞癌A431细胞移植小鼠的SCC治疗。SLURP-1剂量的增加并没有显著提高治疗效率。而与阿霉素联用可进一步增强SLURP-1的抗肿瘤活性,显著抑制肿瘤转移。联合治疗的效果伴随着肿瘤中EGFR表达的下调。SLURP-1可以直接抑制EGFR的激活。联合治疗无毒副作用。我们的数据表明,SLURP-1联合低剂量化疗是一种很有前景的治疗SCC的方法,值得进一步研究。
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来源期刊
Acta Naturae
Acta Naturae 农林科学-林学
CiteScore
3.50
自引率
5.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Acta Naturae is an international journal on life sciences based in Moscow, Russia. Our goal is to present scientific work and discovery in molecular biology, biochemistry, biomedical disciplines and biotechnology. These fields represent the most important priorities for the research and engineering development both in Russia and worldwide. Acta Naturae is also a periodical for those who are curious in various aspects of biotechnological business, innovations in pharmaceutical areas, intellectual property protection and social consequences of scientific progress. The journal publishes analytical industrial surveys focused on the development of different spheres of modern life science and technology. Being a radically new and totally unique journal in Russia, Acta Naturae is useful to both representatives of fundamental research and experts in applied sciences.
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