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亚麻籽油及其与阿霉素联合使用的抗肿瘤作用

Antitumoral Effects of Linseed Oil and Its Combination With Doxorubicin.

作者信息

Shadyro Oleg, Sosnovskaya Anna, Edimecheva Irina, Ihnatovich Lana, Dubovik Boris, Krasny Sergei, Tzerkovsky Dmitry, Protopovich Egor

机构信息

Laboratory of Chemistry of Free-Radical Processes, Research Institute for Physical and Chemical Problems, Belarusian State University, Minsk, Belarus.

Department of Chemistry, Belarusian State University, Minsk, Belarus.

出版信息

Front Pharmacol. 2022 Jun 21;13:882197. doi: 10.3389/fphar.2022.882197. eCollection 2022.

Abstract

Linseed oil (LO) is known for its exceptional nutritional value due to the high content of alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid; its anticarcinogenic effect has been established in several experimental and epidemiological studies. As an adjuvant of chemotherapeutic agents, LO and other ALA-rich vegetable oils have been studied in only a handful of studies at the experimental level. However, the efficacy of antitumoral therapy using doxorubicin (Dox) in combination with ALA and ALA-rich substrates has not yet been investigated. In this work, the antitumor activity of LO in a wide dose range was studied with monotherapy and combined with Dox in animal models with Pliss lymphosarcoma (PLS) and Lewis lung adenocarcinoma (LLC). It was founded the daily oral administration of LO (1, 3, and 10 ml per 1 kg) to rats (PLS) and 6 ml/kg to mice (LLC) for 11-12 days from 7 days after subcutaneous transplantation of tumors has a stable statistically significant effect on the dynamics of tumor growth, reducing the intensity of tumor growth and increasing the frequency of complete tumor regressions (CR) compared with the control. LO showed high antimetastatic activity in the LLC model. Furthermore, LO at a dose of 3 ml/kg potentiates the antitumor effect of Dox in the PLS model, reducing the volume of tumors at the end of treatment by 2.0 times ( = 0.013), the value of the tumor growth index by 1.6 times ( < 0.03) and increasing the frequency of CR 60 days after the start of therapy by 3.5 times ( = 0.019) compared with the use of Dox alone. The combination of Dox and LO or fish oil allows growing efficiency therapy of LLC in comparison with Dox alone, increasing the frequency of CR to 73.68% and 94.4%, respectively, and reducing the frequency of metastasis to zero.

摘要

亚麻籽油(LO)因其富含α-亚麻酸(ALA)而具有极高的营养价值,ALA是一种必需的ω-3多不饱和脂肪酸;其抗癌作用已在多项实验和流行病学研究中得到证实。作为化疗药物的佐剂,LO和其他富含ALA的植物油仅在少数实验水平的研究中被探讨过。然而,阿霉素(Dox)联合ALA及富含ALA的底物进行抗肿瘤治疗的疗效尚未得到研究。在本研究中,我们在患有普利斯氏淋巴肉瘤(PLS)和刘易斯肺癌(LLC)的动物模型中,研究了LO在广泛剂量范围内的单药抗肿瘤活性以及与Dox联合使用的情况。结果发现,从肿瘤皮下移植7天后开始,连续11 - 12天每天给大鼠(PLS)口服LO(每1 kg体重1、3和10 ml),给小鼠(LLC)口服6 ml/kg,与对照组相比,对肿瘤生长动态具有稳定的统计学显著影响,可降低肿瘤生长强度并增加肿瘤完全消退(CR)的频率。在LLC模型中,LO显示出高抗转移活性。此外,在PLS模型中,3 ml/kg剂量的LO可增强Dox的抗肿瘤作用,与单独使用Dox相比,治疗结束时肿瘤体积缩小2.0倍(P = 0.013),肿瘤生长指数值降低1.6倍(P < 0.03),治疗开始60天后CR频率增加3.5倍(P = 0.019)。与单独使用Dox相比,Dox与LO或鱼油联合使用可提高LLC的治疗效果,CR频率分别增加到73.68%和94.4%,转移频率降低至零。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4b9/9254224/3a2f0abdf421/fphar-13-882197-g001.jpg

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