4.7 Article

A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma

Journal

FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.951831

Keywords

hepatocellular carcinoma; single nucleotide mixture; molecular-targeted therapy; tyrosine-kinase inhibitor; immune-checkpoint inhibitor; nutritional and supportive treatment

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This study explored the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of hepatocellular carcinoma (HCC) and investigated its importance as adjuvant therapy. The results showed that compared to a commonly used nutritional supplement, the SNM did not induce metabolic abnormalities in HCC cells and could attenuate lymphocyte injury induced by antitumor drugs, promoting lymphocyte recruitment and survival in HCC tissues. Additionally, the SNM enhanced the anti-tumor activity of molecular-targeted drugs against HCC.
New strategies for molecular-targeted drug therapy for advanced hepatocellular carcinoma (HCC) ignore the contribution of the nutritional status of patients and nutritional support to improve physical status and immunity. We aimed to elucidate the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of HCC, and to explore the importance of a SNM as adjuvant therapy for HCC. Compared with a lipid emulsion (commonly used nutritional supplement for HCC patients), the SNM could not induce metabolic abnormalities in HCC cells (Warburg effect), and did not affect expression of metabolic abnormality-related factors in HCC cells. The SNM could also attenuate the lymphocyte injury induced by antitumor drugs in vitro and in vivo, and promote the recruitment and survival of lymphocytes in HCC tissues. Using HCC models in SCID (server combined immune-deficiency) mice or BalB/c mice, the SNM had anti-tumor activity, and could significantly upregulate the antitumor activity of molecular-targeted drugs (tyrosine-kinase inhibitors [TKI] and immune-checkpoint inhibitors [ICI]) against HCC. We employed research models in vivo and in vitro to reveal the anti-tumor activity of the SNM on HCC. Our findings expand understanding of the SNM and contribute to HCC (especially nutritional support) therapy.

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