Abstract
Objective
Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-α-tocopheryl succinic acid (VES), β-carotene (β-Ca), and L-lysine (Lys).
Methods
The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo.
Results
MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function.
Conclusions
This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
概要
目的
通过手术切除和辅助疗法治疗原发性肿瘤已被广泛研究, 但对于肿瘤转移的有效治疗策略和药物仍然缺乏。本研究中, 我们提出了一种基于组合化合物的功能性产品用作肿瘤辅助治疗, 各化合物机制明确, 可抑制癌症转移、改善抗癌治疗、增**免疫力和抗氧化。该组合由四种廉价化合物组成:L-硒-甲基硒代半胱氨酸(MSC)、D-α-生育酚琥珀酸(VES)、β-胡萝卜素(β-Ca)和赖氨酸(Lys), 命名为MVBL。
方法
通过体外实验研究MVBL对细胞活力、细胞周期、细胞凋亡、细胞迁移、细胞侵袭、活性氧(ROS)和紫杉醇(PTX)联合治疗的影响。在动物水**测定了MVBL在体内的抗氧化和免疫增**能力。通过小鼠肿瘤模型测定MVBL在体内对肿瘤转移的抑制。
结果
MVBL对肿瘤细胞的毒性高于对**常细胞的毒性。它没有显著性地影响癌细胞的细胞周期, 但增加了细胞凋亡。划痕、粘附和侵袭实验结果表明, MVBL显著抑制肿瘤细胞迁移、粘附和侵袭。MVBL使乳腺癌MDA-MB-231细胞对PTX更敏感, 表明它可以作为佐剂来增**化疗药物的治疗效果。小鼠实验数据表明, MVBL可以抑制肿瘤转移, 延长其生存时间, 增**其抗氧化能力和免疫功能。
结论
本研究揭示了MVBL在提高免疫、抗氧化、防止肿瘤生长和抑制体内外转移方面的作用。MVBL可用作癌症治疗的辅助药物, 提高癌症患者的生存率和生活质量。
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 81961138017 and 81703555), the Natural Science Foundation of Fujian Province (Nos. 2021J011046 and 2020J01859), the Young and Middle-aged Teacher Education Research Project of Fujian Province (No. JAT200412), the Science and Technology Planning Projects of Fuzhou (No. 2021S094), the Science and Technology Planning Projects of Fuzhou Institute of Oceanography (No. 2021F08), the Belt & Road Program (No. KXPT-2021-3, CAST), and the Ministry of Science and Technology of China (No. 2015CB931804).
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Yunlong CHENG, Yusheng LU, and Lee JIA planned the study. Yunlong CHENG, Shu LIAN, Shuhui LI, Yusheng LU, Jie WANG, **aoxiao DENG, and Shengyi ZHAI performed cell experiments and collected data. Shu LIAN, Shuhui LI, and Yusheng LU analyzed and interpreted data. Yunlong CHENG, Shu LIAN, and Lee JIA drafted manuscript. All the authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Yunlong CHENG, Shu LIAN, Shuhui LI, Yusheng LU, Jie WANG, **aoxiao DENG, Shengyi ZHAI, and Lee JIA declare that they have no conflict of interest.
All institutional and national guidelines for the care and use of laboratory animals were followed. All animal care and experimental procedures were approved by the Minjiang University Institutional Animal Care and Use Committee (No. 20221114R).
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Cheng, Y., Lian, S., Li, S. et al. Combination of Se-methylselenocysteine, D-α-tocopheryl succinate, β-carotene, and l-lysine can prevent cancer metastases using as an adjuvant therapy. J. Zhejiang Univ. Sci. B 23, 943–956 (2022). https://doi.org/10.1631/jzus.B2200232
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DOI: https://doi.org/10.1631/jzus.B2200232